(Forum for members to discuss the use of anabolic steroids)
New Theory on PCT!
This is really exciting stuff! Keep in mind that this is just a theory right now but his reasoning is very solid IMO. I've bolded what I think is the "Cliff Notes" version for those who don't like reading technical jargon.
Opioid Modulation & Potential for Preventing Anabolic Androgenic Steroids (AAS) Induced HPTA Suppression:
By: Eric M. Potratz
Discussion of pharmaceutical agents below is presented for information only. Nothing here is meant to take the place of advice from a licensed health care practitioner. Consult a physician before taking any medication.
Post Cycle Therapy (PCT) is a key component in a steroid cycle, as suppression of the Hypothalamus, Pituitary, Testicular Axis (HPTA) is seemingly unavoidable to a steroid user. What I will be presenting in this article is a new idea to the world of Anabolic Androgenic Steroids (AAS) users. This exciting new concept addresses the possibility of limiting and possibly preventing suppression of the (HPTA) during cycle. More specifically, we will learn how we can actively modulate the hypothalamus & pituitary pulse generator during cycle and how this can prime our endocrine system for a quicker, smarter, and healthier recovery from anabolic androgenic steroids (AAS).
For a moment, let’s forget the concept of "post cycle therapy", and embrace the idea of "constant cycle therapy" – active therapy throughout a steroid cycle. The HPTA involves a constant biological interplay of responses and feedback loops that can ultimately become shutdown and degraded during exogenous hormone administration. However, research suggests suppression of the hypothalamus and pituitary may be preventable during steroid use. Before we delve into the details, lets first take a quick recap on the HTPA and how it responses to AAS.
HPTA – The basics
When the hypothalamus senses low hormone levels, it secretes gonandotropin releasing hormone (GnRH). This GnRH then travels a short distance to the nearby pituitary gland to stimulate gonadotrope receptors. These, in turn, secrete the gonadotrophins, luteinizing hormone (LH) and follicle stimulating hormone (FSH). These gonadotrophins travel all the way down to the testis, to activate their respective leydig and seritoli cells. LH initiates testosterone production via the leydig cell receptor (steroidogenesis), while FSH initiates sperm production via the sertoli cell receptor (spermatogenesis).
AAS’s inhibit hormone production just as endogenous hormones do. Testosterone interacts with the androgen receptor (AR) and estrogen interacts with the estrogen receptor (ER). When these hormones are in high concentration, they cause the hypothalamus to decrease its release of GnRH, which decreases LH and FSH production from the pituitary.1 This cuts off the signal to the testis and halts all hormone production. This process is a daily event for the rhythmic endocrine system. Spikes in LH & FSH are followed by spikes in testosterone, and spikes in testosterone result in a reduction of LH & FSH release until testosterone levels decline and LH & FSH is released again. The caveat with most steroids, is that hormone levels remain chronically high (24/7) and do not allow release of LH or FSH, thus leaving the pituitary and testis in a dormant state for as long as the steroids are administered.
While low-dose on-cycle hCG is a good protocol to mimic LH and keep the testis from atrophy, (to be covered in a future article) it does nothing to prevent pituitary atrophy. We forget that the pituitary is susceptible to the same degradation and atrophy as the testis. That is, when the GnRH secretion from the hypothalamus stops (during a steroid cycle), the pituitary reduces its number of GnRH receptors and becomes less and less responsive to GnRH stimulation as weeks pass.11 This is analogous to atrophy of the testis, during absence of an LH or FSH signal. On the same accord, both the pituitary and testis will decrease receptor concentration during over stimulation as well, as its been found from too much hCG use or too much GnRH stimulation.12,13 The point here, is that only minor stimulus is required for preservation of function and sensitivity. Perhaps a completely neglected and suppressed pituitary may explain the lack of full and prompt recovery for many steroid users, despite adherence to a "tried and true" hCG, Clomid + Nolvadex regimen. So the question is – How can we prevent suppression of the pituitary, and better yet, how can we prevent suppression of the hypothalamus?
A closer look –
In should be mentioned that another mechanism in which Anabolic Androgenic Steroids (AAS) inhibit LH and FSH release from the pituitary is by direct suppression upon the pituitary GnRH receptors and consequent quenching of LH & FSH secretion.35,38 However its appears that Anabolic Androgenic Steroids (AAS) which bind strictly to the AR, do not exert a direct negative effect on pituitary function or sensitivity.34,37,39 This agrees with the theory that non-aromatizing steroids such as Primobolan, Proviron or Masteron are not nearly as suppressive as an aromatizing AAS’s such as testosterone or Dianabol. Evidence suggests that estradiol is about 200x more suppressive than testosterone on a molar basis37, and that administration of Arimidex can greatly reduce testosterones suppression on GnRH and LH release.42 So, we know anti-estrogens can limit suppression of AAS, but this only solves half the problem.
When it comes to suppression of the hypothalamus, and what seems to be basic endocrinology, we find it is not so simple upon closer examination. There is more than a simple on-off switch for the hypothalamus control center, a lot more. Evidence suggests that there isn’t even a direct AR or ER action upon GnRH release.2-6 That is, steroid hormones do not directly influence GnRH release from the GnRH neurons.7
It was well summarized here by A.J Tilbrook et al,
"It follows, that the actions of testicular steroids on GnRH neurons must be mediated via neuronal systems that are responsive to steroids and influence the activity of GnRH neurons."
And again here by FJ Hayes et al
"It was thus postulated that estrogen-receptive neurons were acting as intermediaries in the non-genomic regulation of GnRH by estrogen"
There is a network of neurogenic intermediaries in the hypothalamus for GnRH release that communicate the inhibitory effects of steroid hormones. More specifically, it is the combined efforts of neuro-active peptides and catecholamines which send the message of "suppression" to the GnRH neurons once activated by steroid hormones.16 These primary messengers are known as a group of neuro-active peptides called endogenous opioid peptides (EOP’s).7,16 The EOP’s consist of the three main peptides -- b-endorphin, dynorphin, and enkephalins, which act upon their respective u-opioid, k-opioid, and s-opioid receptors. It appears that the most influential EOP in GnRH modulation is b-endorphin, acting upon the u-opioid receptor. 8-10 For this reason, b-endorphin will be the main focus of the article, although there are other intermediates involved.
When steroid hormones reach the hypophysial portal, they activate the EOP’s, which suppress GnRH. We know that steroid hormones must communicate with these opioid receptors in order for them to inhibit the release of GnRH from the GnRH neurons, since the GnRH neurons do not have AR or ER receptors. What’s most interesting here is that the suppression on GnRH neurons can actually be intercepted by a u-opioid receptor antagonist – such as naloxone, and the orally active congers naltrexone, and nalmefene.
This is accomplished by blocking the u-opioid receptor and preventing the inhibitory effects of b-endorphin upon the GnRH releasing neuron. It should be noted that this "antagonism" of suppression is not due to antagonism of the AR or ER itself, since u-opioid antagonists to not bind to these hormone receptors.15,32
The effect of a u-opioid receptor antagonist on the HPTA can be seen here --(See Attachment)
Essentially, a u-opioid antagonist such as naloxone takes the brakes off of GnRH release and allows pulses of GnRH to occur as if no steroid hormones are present.17 Naloxone, and related u-opioid antagonists have consistently proven to block the suppressive effects of testosterone, DHT, and estrogen administration in both animals and humans.18-25 It also appears that these drugs have the ability to increase pituitary sensitivity to GnRH.26,27
U-opioid antagonists have long been used for treatment of opioid dependence; not only to control cravings of narcotics, but to restore a suppressed endocrine system.28,29 It’s well known that strong opioid based drugs such as methadone, cocaine, heroin and alcohol can suppress GnRH and therefore suppress LH & FSH. It seems that this decease of GnRH is due to the same EOP mechanisms seen with Anabolic Androgenic Steroids (AAS) induced suppression.33 In alcoholics, cocaine and heroin users, naltrexone and naloxone have been used to restore LH and testosterone levels.28,29 Naltrexone has even been proposed as a treatment for male impotence and erectile dysfunction.30,31
Naloxone, naltrexone and nalmefene seem progressively more powerful in their potency to dis-inhibit LH release, respectively14,18 Naloxone lacks oral bioavailability therefore injection is required. An injectable preparation could easily be made with BA water due to the water solubility of the compound. A 40mg subcutaneous injection would be a typical dose of naloxone. Naltrexone is orally active, with a safe and effective oral dose being about 100mg for a 220lb male.18 While a lower dose of about 25-50mg of nalmefene would seemingly have the same benefit.20,24 Increasing the dose with either of these drugs will surely increase the likelihood of side-effects without notably increasing the benefit. An every 3rd day protocol would seem appropriate with these drugs, as only to increase GnRH and LH release enough to prevent pituitary and testicular shrinkage – Just enough to keep them in the "ball game". Also, a twice a week dosing protocol would most likely limit the increased opioid sensitivity induced by the long-term use of the drugs.
A word of caution: The opioids antagonists mentioned in this article are recognized as safe and non-toxic at the given dosages, however they can cause severe withdrawal symptoms in opiate users (methadone, morphine, cocaine, and heroin addicts.) Caution is also advised when using opioid antagonists prior to sedation or surgery as they can reduce effectiveness of anesthetics. Temporary nausea, headache or fatigue, are occasional side-effects associated with the use of these drugs. Naltrexone has been reported to heighten liver enzymes, while naloxone and nalmefene do not appear to have this issue. At any rate, a twice a week protocol for 4-16 weeks is unlikely to cause any liver issues that may be associated with naltrexone.
A few point to consider -
For those who choose to embark on a every 3rd day protocol of an opioid antagonist several things should be considered. First, total prevention of HPTA suppression is unlikely in a cycle of 1gm or more per week of AAS. However, by following smart cycling guidelines, suppression will at least be minimized to the point where normal HPTA function could be regained within days of Anabolic Androgenic Steroids (AAS) clearance, rather than months. The protocol suggested in this article would at least allow steroid users to limit the usage of classic SERM’s for post cycle therapy (pct), as these drugs can have obvious undesired effects. Several things shall be considered when planning an Anabolic Androgenic Steroids (AAS) protocol designed to limit suppression.
It appears that progestin based Anabolic Androgenic Steroids (AAS) such as trenbolone and nandrolone which bind not only to the AR, but also to the progesterone receptor (PR) also have a directly suppressive effect on pituitary sensitivity36 (similar to estrogens). It also appears that no opioid receptor antagonist or anti-aromatase can prevent suppression via the PR. Therefore, a multiple gram stack of testosterones and nandrolones is no doubtingly going to completely suppress HTPA function by causing suppression via the ER, AR and PR.40,41 If one hopes for a prompt and full recovery post cycle, perhaps nandrolones are better avoided, or at least not stacked with heavily aromatizing Anabolic Androgenic Steroids (AAS) without the concurrent use of a strong AI.
As it was pointed out earlier in this article, estrogen has a markedly stronger effect on suppression of LH release compared to androgens since estrogens suppresses the hypothalamus and pituitary. Usage of an Aromatase inhibitor (AI) such as anastrozole, letrozole, or exemestane (Aromasin) can reduce estrogen and greatly reduce suppression on GnRH, LH and FSH release by preventing excessive ER activation in the hypothalamus and desensitization of the pituitary gonadotropes. 35,37,38 Anastrozole has ~50% maximal total estrogen suppression at 1mg/day. Exemestane has ~50% maximal total estrogen suppression at 25mg/day. While letrozole has ~60% at 1mg/day. These are averages based on compiled data from several studies. Similar estrogen suppression can also been seen from only twice a week administration of these AI’s.43-47
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5. Unmasking the neural progesterone receptor in the preoptic area and hypothalamus of the ewe: no colocalization with gonadotropin-releasing neurons. Skinner DC, Caraty A, Allingham R. Endocrinology 2001; 142:573–579.
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8. Steroid Control of Gonadotropin-Releasing Hormone Secretion: Associated Changes in Pro-Opiomelanocortin and Preproenkephalin Messenger RNA Expression in the Ovine Hypothalamus
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10. -Endorphin blocks luteinizing hormone-releasing hormone release by inhibiting the nitricoxidergic pathway controlling its release. Alicia G. Faletti, Claudio A. Mastronardi, Alejandro Lomniczi, Adriana Seilicovich, Martha Gimeno, Samuel M. McCann, and Valeria Rettori. PNAS, Feb 1999; 96: 1722.
11. The frequency of gonadotropin-releasing hormone stimulation determines the number of pituitary gonadotropin-releasing hormone receptors. Katt JA, Duncan JA, Herbon L, Barkan A, Marshall JC. Endocrinology. 116:2113–2115. (1985)
12. Exogenous gonadotrophin-releasing hormone (GnRH) stimulates LH secretion in male monkeys (Macaca fascicularis) treated chronically with high doses of a GnRH-antagonist. Weinbauer GF, Hankel P, Nieschlag E. J Endocrinol. 133:439–445. (1992)
13. Chronic administration of the luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix decreases gonadotrope responsiveness and pituitary LHRH receptor messenger ribonucleic acid levels in rats. Pinski J, Lamharzi N, Halmos G, et al. 1996. Endocrinology. 137:3430–3436.
14. Acute effects of testosterone infusion and naloxone on luteinizing hormone secretion in normal men.
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15. Naloxone-induced increases in serum luteinizing hormone in the male: mechanisms of action
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16. Endogenous opioids participate in the regulation of the hypothalamic-pituitary-luteinizing hormone axis and testosterone’s negative feedback control of luteinizing hormone. CICERO, T. J., SCHAINKER, B. A. AND MEYER, E. R. Endocrinology 104: 1286-1291, (1979)
17. Opiatergic control of LH secretion is eliminated by gonadectomy. BHANOT, R. AND WILKINSON, M.: Endocrinology 112: 399-401, (1983)
18. Role of endogenous opiates in the expression of negative feedback actions of androgens and estrogen on pulsatile properties of luteinizing-hormone secretion in man. Veldhuis JD, Rogol AD, Samojlik E, Ertel MH. J Clin Invest. 74:47–55 (1984)
19. Counteraction of gonadal steroid inhibition of luteinizing hormone release by naloxone. VAN VUGT, D. A., SYLVESTER, P. W., AYLSWOWRH, D. F. AND MNRRAS J. J. Chro- naloxone. Endocrinology 34: 274-278, 1982
20. Unexpected effects of nalmefene, a new opiate antagonist, on the hypothalamic-pituitary-gonadal axis in the male rat. P Limonta, CW Bardin, EF Hahn, and RB Thau. Steroids, Dec 1985; 46(6): 955-65.
21. In vivo evidence for a direct effect of naloxone on testicular steroidogenesis in the male rat. TJ Cicero, ML Adams, LH O'Connor, and B Nock. Endocrinology, Aug 1989; 125: 957
22. Endogenous opioids participate in the regulation of the hypothalamus- pituitary-luteinizing hormone axis and testosterone's negative feedback control of luteinizing hormone. TJ Cicero, BA Schainker, and ER Meyer. Endocrinology, May 1979; 104: 1286
23. Effect of naloxone on the plasma levels of LH, FSH, prolactin and testosterone in Beetal bucks.
Singh B, Dixit VD, Singh P, Georgie GC, Dixit VP. Department of Animal Production Physiology, CCS Haryana Agricultural University, 125004, Hisar, India
24. Endocrinology: The effect of nalmefene on pulsatile secretion of luteinizing hormone and prolactin in men. G.R. Graves, T.G. Kennedy, R.F. Weick, and R.F. Casper. Hum. Reprod., Oct 1993; 8: 1598 - 1603.
25. Effects of the novel opiate antagonist, SDZ 210-096, on luteinizing hormone secretion in the rat
RA Siegel and L Revesz. J. Pharmacol. Exp. Ther., Apr 1989; 249: 264.
26. Effect of antagonists of dopamine and opiates on the basal and GnRH-induced secretion of luteinizing hormone, follicle stimulating hormone and prolactin during lactational amenorrhoea in breastfeeding women. C.C.K. Tay, A.F. Glasier, and A.S. McNeilly. Hum. Reprod., Apr 1993; 8: 532 - 539.
27. Naltrexone administration modulates the neuroendocrine control of luteinizing hormone secretion in hypothalamic amenorrhoea. Alessandro D. Genazzani, Mario Gastaldi, Felice Petraglia, Cesare Battaglia, Nicola Surico, Annibale Volpe, and Andrea R. Genazzani. Hum. Reprod., Nov 1995; 10: 2868 - 2871.
Revives LH and testosterone in heroin users
28. Heroin and naltrexone effects on pituitary-gonadal hormones in man: interaction of steroid feedback effects, tolerance and supersensitivity. JH Mendelson, J Ellingboe, JC Kuehnle, and NK Mello. J. Pharmacol. Exp. Ther., Sep 1980; 214: 503.
29. Alcohol effects on luteinizing hormone and testosterone in male macaque monkeys. NK Mello, JH Mendelson, MP Bree, J Ellingboe, and AS Skupny. J. Pharmacol. Exp. Ther., Jun 1985; 233: 588.
Opioid antagonist enhances erectile function
30. Erectile function and naltrexone. Goldstein JA. Ann Intern Med 105:799 (1986)
31. Opiate antagonists in erectile dysfunction: a possible new treatment option? Results of a pilot study with naltrexone. van Ahlen H, Piechota HJ, Kias HJ, Brennemann W, Klingmuller D. Eur Urol 28:246–250 (1995)
32. The effects of opiates on androgen binding in the forebrain of the rat. PJ Sheridan and JM Buchanan
Int J Fertil, January 1, 1980; 25(1): 36-43. 33. Morphine exerts testosterone-like effects in the hypothalamus of the castrated male rat. CICERO, T. J., MEYER, E. R., GABRIEL, S. M., BELL, R. D. AND WILCOX, C. E. Brain Rae. 202: 151-164, (1980)
DHT and testosterone not suppressive to the pituitary like estrogens
34. Studies of gonadotropin-releasing hormone (GnRH) action using GnRH receptor-expressing pituitary cell lines. Kaiser UB, Conn PM, Chin WW. Endocr Rev. 18:46–70. (1997)
Estrogen decreases gonadotrope receptors for GrRH.
35. Patterns of LH secretion in castrated bulls during intravenous infusion of androgenic and estrogenic steroids: Pituitary response to exogenous luteinizing hormone-releasing hormone. M.J. D’occhio et al. Biology of reproduction 26, 249-257 (1982)
36. Demonstration of progesterone receptor mediated gonadotrophin suppression in men. Brady B, Anderson RA, Kinniburgh D, Baird DT 2002. J Endocrinol 3(Suppl):OC37
37. Bagatell CJ, Dahl KD, Bremner WJ. 1994 The direct pituitary effect of testosterone to inhibit gonadotropin secretion in men is partially mediated by aromatization to estradiol. J Androl. 15:15–21.
38. Sherins RJ, Loriaux DL. 1973 Studies on the role of sex steroids in the feedback control of FSH concentrations in men. J Clin Endocrinol Metab. 36:886–893
39. Santen RJ. 1975 Is aromatization of testosterone to estradiol required for inhibition of luteinizing hormone secretion in men? J Clin Invest. 56:1555–1563
40. Influence of nandrolondecanoate on the pituitary-gonadal axis in males. JW Bijlsma, SA Duursma, JH Thijssen, and O Huber. Acta Endocrinol (Copenh), September 1, 1982; 101(1): 108-12.
Both progestin (nandrolone) and testosterone more effective at reducing LH/FSH and causing azoospermia.
41. Endocrine approaches to male fertility control. UA Knuth and E Nieschlag; Baillieres Clin Endocrinol Metab, February 1, 1987; 1(1): 113-31.
42. Aromatization Mediates Testosterone's Short-Term Feedback Restraint of 24-Hour Endogenously Driven and Acute Exogenous Gonadotropin-Releasing Hormone-Stimulated Luteinizing Hormone and Follicle-Stimulating Hormone Secretion in Young Men. J. A. Schnorr, M. J. Bray, and J. D. Veldhuis
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GREAT read. One question that came up for me: When they say "Also, a twice a week dosing protocol would most likely limit the increased opioid sensitivity induced by the long-term use of the drugs." They are referring to the steroid's ability to suppress the HPTA only and not the ability to bind to the AR correct?
Mmmm interesting read, didn't realise the pituitary atrophied too!
- Rep Power
Well many people will become addicts because have you tried that drug? i have and i have friends that are ex heroinaddicts and when you take it its just like taking heroin and this goes for people that dont use it every day.
People that are drugaddicts their bodys can take alot higher doses but even they say that the first weeks ,maybe 1-3 weeks they feel like they are on heroin then the drug gets stable in the body and they dont get that effect nomore but normal people would get high like on heroin so its a big gamble what if you like it to much?
Like i said i tried it and i almost got addicted to it ,here in sweden we have that drug its sold under the name "suboxone" and it contains buprenorphine and naloxone
And its pure BS that its non-toxic and not dangerous to the liver,i know people that have died from livercomplications of that drug and we have a site in sweden www.fass.se where all drugs that are sold in sweden are listed ,doctors use this site also to read about drugs when they prescribe and it clearly states that you should check the liverenzymes before you start using the drug and people with existing liverproblems may have even bigger problems using this drug.
Problem is that "suboxone"also contains buprenorphine and its also known to be very dangerous on the liver ,in france where this drug has been used alot people have died from livercomplications and when you read about this drug it says: Patients have gotten hepatis with livernecrosis(the liver tissue is rotting) and the manufacturer doesent know why this happends!
Non toxic my ass
thanks for the counter bmass!
One can easily find a pure form of the drug, generics are available as well. A non-addict will NOT a) become addicted and b) get a "high" from this drug. Also, I'd estimate about 90% of oral meds have a recommendation for having a liver panel done before administration. Also, keep in mind that for our purposes one would be taking a lower dose and for shorter duration than an addict would be.
Originally Posted by bmass
- Rep Power
What if it was given IV, what kind of dosing schedule would be needed for Naloxone? 40 mg SubQ sounds a little high, 2-10mg IV is enough to bring just about any heroin addict out of their high.
- Rep Power
Originally Posted by DocJ
The narcotic antagonist naloxone was studied in man to determine if it produced behavioral effects and physical dependence and if it substituted for morphine in morphine-dependent subjects. When compared to placebo in 12 subjects in a cross-over design, no or little activity was demonstrated for naloxone while, in contrast, the narcotic antagonists, nalorphine and levallorphan, constricted pupils, produced responses on the subject's and observer's single-dose opiate questionnaires and produced psychotomimetic and sedative-like responses in a "subjective drug effect" questionnaire. In 10 subjects, naloxone administered 1, 2 and 4 hr before a test dose of morphine antagonized the effects of morphine. In morphine-dependent subjects, naloxone was 7 times as potent as nalorphine in precipiting abstinence. In three subjects, no behavioral or physiologic changes were observed during chronic administration and withdrawal of naloxone; however, the ability of naioxone to antagonize the effects of a test dose of morphine persisted. It is concluded that naloxone does not have abuse potential of the morphine type since it does not produce subjective effects or physical dependence and precipitates abstinence in morphine-dependent subjects. Further, naloxone is distinguished from the narcotic antagonists, nalorphine, levallorphan and cyclazocine, in that it does not constrict pupils or produce subjective effects, physical dependence or tolerance.
In a few months they'll have a new theory. Ive stuck to my protocol for yrs without any problems and dont plan on changing what works for me.
To each their own....
Good read though.
Tell us something we don't know.
Originally Posted by gator_mclusky
- Rep Power
In the article it mentions : " Usage of an Aromatase inhibitor (AI) such as Anastrozole, letrozole, or exemestane (Aromasin) can reduce estrogen and greatly reduce suppression on GnRH, LH and FSH release by preventing excessive ER activation in the hypothalamus and desensitization of the pituitary gonadotropes. 35,37,38"
But what about using Nolvadex during cycle as an anti-estrogen? Would this work similar to the ones he mentions in the paragraph above? Or does Nolva work different that those mentioned??
the article contains a number of innaccuracies and uses faulty models especially when it comes to exogenous androgens and aromatase inhibition, its also really just part of an advertisement.
Nolva only blocks estrogen from certain receptors. The others work to eliminate it alltogether. So I don't believe nolva would work for this purpose.
Originally Posted by whoopas5
an advertisment for what?
Originally Posted by macro
two strong refutations of the primary claim of this "article"
1: J Clin Endocrinol Metab. 1994 Oct;79(4):1147-51. Links
Nocturnal naloxone fails to reverse the suppressive effects of testosterone infusion on luteinizing hormone secretion in pubertal boys.Kletter GB, Foster CM, Brown MB, Beitins IZ, Marshall JC, Kelch RP.
Department of Pediatrics, University of Michigan, Ann Arbor 48109.
LH secretion is maximal during the night in pubertal boys, and testosterone (T) administration blunts this nocturnal rise of LH. We have previously shown that in pubertal boys, the acute negative feedback effects of T infusion on LH secretion during the daytime cannot be reversed by opioid receptor blockade. To determine whether the nocturnal secretion of LH in early puberty is regulated by endogenous opioid pathways, we determined whether naloxone during the night affected LH secretion or T-mediated suppression of LH secretion. Seven pubertal boys (bone age, 11-13.5 yr) were given a control infusion of saline, followed 1 week later by an infusion of T at 960 nmol/m2.h for 41 h starting at 2000 h. During both saline and T infusions, six iv boluses of saline were given hourly beginning at 2400 h on the first day, and six iv boluses of naloxone (0.1 mg/kg each) were given hourly beginning at 2400 h on the second day. Starting at 2200 h, blood was obtained every 15 min for LH and every 30 min for T determinations for 14 h each night. Pituitary responsiveness was assessed at the end of each study night by i.v. bolus administration of 250 ng/kg synthetic GnRH. T infusion increased the mean T concentration 6-fold (P < 0.0001) and suppressed the mean plasma LH concentrations from 5.6 +/- 0.6 to 3.8 +/- 0.6 IU/L (P < 0.01). The nocturnal augmentation of LH secretion was suppressed by the infusion of T, and this suppression was not reversed by naloxone. The mean nighttime plasma LH (2400-0600 h) was 8.1 +/- 1.1 IU/L during the control saline infusion and 5.1 +/- 0.6 IU/L during the T infusion (P < 0.01). The mean LH level was 4.0 +/- 0.7 IU/L during the administration of naloxone boluses concomitantly with the T infusion, not significantly different from that during the T infusion. Likewise, LH pulse frequency during the same time period was decreased by T infusion from 0.6 +/- 0.1 to 0.36 +/- 0.04 pulses/boy.h (P < 0.05), and it was unaltered by coadministration of naloxone (0.38 +/- 0.12 pulses/boy.h). Naloxone administration during the saline infusion did not increase either the mean plasma LH concentration (7.5 +/- 0.7 IU/L; P = NS vs. saline control) or the LH pulse frequency (0.69 +/- 0.1 pulses/boy.h; P = NS vs. saline control). Pituitary responsiveness to GnRH was similar on each of the 4 nights during either saline or T infusions.(ABSTRACT TRUNCATED AT 400 WORDS)
1: J Clin Endocrinol Metab. 1997 Dec;82(12):4010-4. Links
Acute effects of estradiol infusion and naloxone on luteinizing hormone secretion in pubertal boys.Kletter GB, Padmanabhan V, Beitins IZ, Marshall JC, Kelch RP, Foster CM.
Department of Pediatrics, University of Michigan, Ann Arbor 48105, USA.
We have shown previously in pubertal boys that testosterone (T) suppresses the nocturnal augmentation of luteinizing hormone (LH) secretion principally by decreasing LH pulse frequency. As T can be aromatised to estradiol (E2), and E2 effects on LH secretory dynamics may be separate from those of T, we examined the effects of acute E2 infusion on LH secretion in pubertal boys. Opioid receptor blockade has been reported to increase LH secretion after estradiol suppression in adult men, so we also examined whether naloxone might augment LH secretion during E2 treatment in pubertal boys. Starting at 1000 h, eight pubertal boys were given a 33 h saline infusion, followed 1 week later by an E2 infusion at 4.6 nmol/m2/h. During both infusions, four iv boluses of saline were given hourly beginning at 1200 h on the first day, and four naloxone iv boluses, 0.1 mg/kg each, were given hourly beginning at 1200 h on the second day. Blood was obtained every 15 min for LH, and every 60 min for T and E2, from 1200 h until the end of the infusion. Pituitary responsiveness to gonadotropin-releasing hormone (GnRH) was assessed after both infusions by iv administration of 250 ng/kg synthetic GnRH. Estradiol infusion increased the mean plasma E2 concentration from 23 +/- 4 to 46 +/- 6 pmol/L (P < 0.01) and suppressed mean plasma T from 4.9 +/- 1.4 to 3.0 +/- 3.5 nmol/L (saline vs. E2 infusion, P < 0.05). The overall mean LH was suppressed by E2 infusion from 3.7 +/- 0.5 to 2.2 +/- 0.4 IU/L (saline vs. E2 infusion, P < 0.01). LH pulse frequency was suppressed by 50%, whereas mean LH pulse amplitude was not different between saline and E2 infusions. Administration of naloxone did not alter the mean LH, LH pulse frequency, or amplitude during either saline or E2 infusions. Pituitary responsiveness to exogenous GnRH was similar during both infusions. These studies indicate that E2 produces its negative feedback in pubertal boys principally by suppression of LH pulse frequency, and naloxone does not reverse these suppressive effects. Thus E2 suppression of LH secretion is mediated by a decrease of hypothalamic GnRH secretion that is independent of endogenous opioid pathways.
Just about everything does, brain, liver, etc
Originally Posted by Lucky13
He who overcomes others has force; He who overcomes himself is strong. Lao-tzu
Thats a very braod statement. Can you break it down for us please?
Originally Posted by LiftTillIDie
Thanks in advance.
No. I answered his question adequately.
Originally Posted by gator_mclusky
Please elaborate how these studies would apply to the average "Joe Blow" cycling aas?
Originally Posted by macro
Also, I'm pretty sure the author of the article isn't selling Naloxone
A very intelligent bro over on CEM possibly suggested a better alternative.
The thread was about people using HGH but I'm wondering if this would apply to an Anabolic Androgenic Steroids (AAS) cycle as well? Someone smarter than I am needs to evaluate this...
Originally Posted by oswaldosalcedo:
naltrexone causes hypothalamic-pituitary-adrenal axis activation (cortisol release). this is not good as cortisol is elevated post cycle already
T4 is the answer. possibly d/t T3 increasing a lot post cycle?
Nandro produces hypothyroidism, GH too, GH increases T4 to T3 conversion,then there is a T4 deficit (Hypothyroidism).
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Inverse control of prolactin and growth hormone gene expression: effect of thyroliberin on transcription and RNA stabilization.
Laverriere JN, Morin A, Tixier-Vidal A, Truong AT, Gourdji D, Martial JA.
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Prolactin dysregulation in women with subclinical hypothyroidism: effect of levothyroxine replacement therapy.
Meier C, Christ-Crain M, Guglielmetti M, Huber P, Staub JJ, Muller B.
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Differential regulation of pituitary hormone secretion and gene expression by thyrotropin-releasing hormone.
Kanasaki H, Yonehara T, Yamamoto H, Takeuchi Y, Fukunaga K, Takahashi K, Miyazaki K, Miyamoto E.
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PreproThyrotropin-Releasing Hormone178-199 Affects Tyrosine Hydroxylase Biosynthesis in Hypothalamic Neurons: A Possible Role for Pituitary Prolactin Regulation.
Goldstein J, Perello M, Nillni EA.
because they directly contradict the claims that naloxone maintains LH and GnRH in the presence of exogenous androgens or estrogens. So it would directly apply to "joe blow" Anabolic Androgenic Steroids (AAS) user.
Originally Posted by DocJ
basically the article is pretty much worthless.
It gives only a minimal nod, an after thought, to aromatase inhibitors. Which is the only reason its not completely worthless.
Fair enough but what about post-cycle?
Originally Posted by macro
Originally Posted by macro
The key word you missed in those studies is “pubertal boys”. The endocrine system works quite differently past puberty. The protocol I outlined will work while on cycle. It has little use for PCT.
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