Post Cycle Therapy (PCT)

[Millard Baker]

After a cycle, we have one goal: to hold onto the gains we made during the cycle. Unfortunately, this is easier said than done, because the levels of various hormones and other substances that were circulating around your body during the cycle (huge amounts of testosterone, Insulin-Like Growth Factor, Growth Hormone, and lower amounts of muscle-wasting glucocorticoids) are now changing. Sadly, they are making way for lower amounts of the hormones we want for building muscle, and higher amounts of the catabolic ones. What needs to be done, as quickly as possible, is to get your body to begin production of your own natural anabolic hormones, and produce less of the catabolic ones. Unfortunately, your body has other plans.

But then, so do I…

http://www.mesomorphosis.com/article...le-therapy.htm

[JoeyNess]

great pct chart

[hooker]

Yeah...like I said, thats basically the extent of my computer abilities...so now, at least when a million geeks steal the article and post it on their own site, they have to at least admit to not being very good with computers also....

[Bob Smith]

Originally Posted by hooker

Yeah...like I said, thats basically the extent of my computer abilities...so now, at least when a million geeks steal the article and post it on their own site, they have to at least admit to not being very good with computers also....

Your recommendation is 500iu/day of HCG. After reading Swales posts for a while, he recommends typically no more than 250iu about every other day, and that higher doses only serve to be counter-productive. Your response to that?

[hooker]

I endevored to answer that particular question within the PCT article itself, because whenever I suggest HCG for PCT Swale's name is brought up. I think that I have shown sufficient evidence for HCG use in PCT, given my suggestion of including Nolvadex to stop the HCG from inhibiting testosterone production. HCG's suppressive effect on endogenous testosterone would appear to be due to to HCG actually blocking the conversion of 17 alpha-hydroxyprogesterone (17 OHP) into testosterone. Nolvadex stops this blocking mechanism from happening. In addition adding the Aromasin ought to stave off any estrogenic based testosterone inhibition.

It's very aggressive, yes. But remember, SWALE's protocol is for HRT and related, while mine is aimed at the competitive athlete and bodybuilder. Hence, his is a bit more safe and conservative, while mine is a bit more aggressive.

But I think I've provided ample evidence for it's efficacy, and before you ask, yes, it's been given successful test runs.

[Bob Smith]

Thanks for the clarification.

At the time, I didnt feel like reading the entire article, so I jumped down to the conclusion and actual protocol.

[jb55638]

ANy one know of a local source for aromasin??
dutchez12@cyber-rights.net

[hooker]

www.ag-guys.com

[RhinoChaser48]

Hooker - a couple initial thoughts:

First I'd like to say great article. Hopefully I don't come off as an ass here because I'm trying to be constructive.

Lets solve that pesky estrogen problem now….

Lets add in an Aromatase Inhibitor! Which one, though? Well, since we are already using Nolvadex, we can’t use Letrozole or Arimidex, as the Nolvadex will actually greatly decrease the blood plasma levels of them (28)!

There isn't any evidence that anastrozole interacts with nolvadex. Only letrozole has been shown to interact. The combined application of letrozole and nolvadex lowers letrozole blood concentration, but the majority is still active in the blood stream. Since letrozole is so powerful, I'm pretty sure you could still use it successfully as you suggested for PCT. Because we don't actually want total suppression of estrogen, do we?


I don't have access to the full text of citation number 27 right now, but I think it is highly optimistic to believe vitamin E will have any significant effect for PCT outside of preventing deficiency, (which can be done with any multi-vitamin and healthy diet).

I believe there are studies that show vitamin E can have the opposite effect as the one your citation states as well, (which might be dose dependent, or related to the type of vitamin E).

Since that study was done in 1982, I think it's probably safe to assume the type of vitamin E was alpha tocopherol. There have been many studies that show supplementing alpha tocopherol by itself causes an imbalance of the other members of the vitamin E family, and other studies that show each member have unique functions not shared by other vitamin E members.

What I'm getting at is this: just because vitamin E plays a role in regulating the endochrine system (which isn't fully understood) doesn't mean supplementing more will mean greater output.

But then again, you might be right. I'm not an expert.

Again, great article.

[hooker]

Originally Posted by RhinoChaser48

Hooker - a couple initial thoughts:

There isn't any evidence that anastrozole interacts with nolvadex.

Sure there is. It's a 27% reduction in anastrozole levels. And although this may not be significant in Breast Cancer survival rates, I feel it to be significant with regards to optimizing our recovery as quickly as possible post-cycle, especially since we are trying to fight the estrogen increase we'll get with the aggressive HCG therapy I suggest:


1: Br J Cancer. 2001 Aug 3;85(3):317-24.Related Articles, Links
Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-protocol of the 'Arimidex and tamoxifen alone or in combination' (ATAC) trial.

Dowsett M, Cuzick J, Howell A, Jackson I; ATAC Trialists' Group.

CRC and UCL Cancer Trials Centre, University College London, Stephenson House, 158-160 N Gower Street, London, NW1 2ND, UK.

The ATAC trial evaluates in a randomized, double-blind design, Arimidextrade mark (anastrozole) alone or in combination with tamoxifen, relative to tamoxifen alone as 5-year adjuvant treatment in postmenopausal women with early breast cancer. Patients included in the pharmacokinetic (PK) sub-protocol had been in ATAC for > or =3 months, taking their medication in the morning and were 100% compliant for the preceding 14 days. Blood samples were collected 24 +/- 4 h after last dose. Trough (C(min)) plasma concentrations of anastrozole, tamoxifen and desmethyltamoxifen (DMT) were measured by validated methods. The PK results were based on a total of 347 patients (131 anastrozole (1 mg o.d.), 111 tamoxifen (20 mg o.d.), 105 anastrozole and tamoxifen (1 and 20 mg o.d. respectively)). The geometric mean steady-state trough plasma concentrations of tamoxifen and DMT were statistically equivalent in patients receiving tamoxifen alone or in combination with anastrozole: geometric mean tamoxifen = 94.8 ng ml(-1)and 95.3 ng ml(-1)in tamoxifen alone and combination groups, respectively; geometric mean DMT = 265.1 and 277.6 ng ml(-1)in the tamoxifen and anastrozole and tamoxifen groups, respectively. The geometric mean anastrozole levels were 27% lower (90% Cl 20-33%;P< 0.001) in the presence of tamoxifen than with anastrozole alone. Baseline plasma oestradiol levels were not obtained in the PK sub-protocol, however, such information was available from a similar ATAC sub-protocol, which evaluated bone mineral density. Mean oestradiol levels were 21.3, 19.3, and 21.6 pmol l(-1)prior to treatment and 3.7, 20.9 and 3.6 pmol l(-1)after 3 months in the anastrozole, tamoxifen, and combination groups, respectively (n = 167). On-treatment values were below the detection limit (3 pmol l(-1)) in 43.6 and 38.5% of the anastrozole alone and anastrozole in combination with tamoxifen groups, respectively. As a result of (a) the lack of effect of anastrozole on tamoxifen and DMT levels and (b) the observed fall in blood anastrozole levels having no significant effect on oestradiol suppression by anastrozole, we conclude that the observed reduction in anastrozole levels by tamoxifen is unlikely to be of clinical significance when anastrozole and tamoxifen are administered together. Copyright 2001 Cancer Research Campaign.

The combined application of letrozole and nolvadex lowers letrozole blood concentration, but the majority is still active in the blood stream. Since letrozole is so powerful, I'm pretty sure you could still use it successfully as you suggested for PCT

Successfull? Maybe. Optimal? No. Letrozole combined with Nolvadex, when it comes to preventing aromatase expressed tumor growth, is no better than Letrozole alone. I don't like that interaction, personally, because it basically makes letrozole + nolvadex only as effective as nolvadex alone (why bother with the letro?)...and I feel it to be far less than optimal, especially when we have aromasin:

J Steroid Biochem Mol Biol. 2005 May;95(1-5):41-8.Related Articles, Links

Model systems: mechanisms involved in the loss of sensitivity to letrozole.

Brodie A, Jelovac D, Sabnis G, Long B, Macedo L, Goloubeva O.

Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Health Science Facilities 1, Room 580, 685 West Baltimore Street, Baltimore, MD 21201, USA. abrodie@umaryland.edu

A number of models have been used to study the development and treatment of breast cancer. Since most breast cancer patients are postmenopausal and treated with hormone therapy, we developed a model to simulate this type of patient. Tumors of human estrogen receptor (ER)-positive breast cancer cells transfected with aromatase (MCF-7Ca) are grown in immune suppressed mice. In this model, we have explored a number of strategies to optimize the antitumor efficacy of treatment such as combining the non-steroidal aromatase inhibitor letrozole with the antiestrogens, tamoxifen. This combination resulted in tumor suppression similar to the antiestrogen alone, but was less effective than letrozole alone. Clinical findings with the non-steroidal inhibitor anastrozole in combination with tamoxifen (ATAC trial) were consistent with our results. Although letrozole was the most effective single agent tested in the model, tumors ultimately began to grow during continued treatment. To investigate the mechanisms by which tumors adapt to growth during letrozole treatment, we determined the expression of signaling proteins in tumors during the course of letrozole treatment compared to the tumors of control mice. We found that tumors initially up regulated the ER, but subsequently receptor levels decreased in tumors unresponsive to letrozole. Adapter proteins (p-Shc and Grb-2) as well as all of the signaling proteins in the MAPK cascade (p-Raf, p-Mek1/2, and p-MAPK), but not Akt, were increased in tumors no longer responsive to letrozole. The results suggest that tumor cells adapt to estrogen deprivation during letrozole treatment by activation of alternate signaling pathways to increase transcription. When letrozole was combined with the pure antiestrogen fulvestrant, to down regulate ER, the combination was more effective than either letrozole or fulvestrant alone. Tumors regressed by 45% and were maintained without growth for the duration of the experiment (29 weeks). Down regulation of ER by fulvestrant may prevent cross talk between these signaling pathways. The results suggest that achieving more complete estrogen blockade may delay development of hormone-independent signaling pathways regulating proliferation.

I think it is highly optimistic to believe vitamin E will have any significant effect for PCT outside of preventing deficiency, (which can be done with any multi-vitamin and healthy diet).

Since we're using HCG in our PCT regimen, and Vitamin E increases the body's plasma testosterone response to HCG, I think it's beneficial for PCT.

Endocrinol Jpn. 1982 Jun;29(3):287-92.Related Articles, Links

Effect of vitamin E on function of pituitary-gonadal axis in male rats and human subjects.

Umeda F, Kato K, Muta K, Ibayashi H.

The role of vitamin E in the endocrine system, in particular the pituitary-gonadal axis, was studied in humans and male rats by examining the hormonal differences between vitamin E deficient and supplemented conditions. In vitamin E deficient rats, pituitary content and basal plasma level of FSH and LH were significantly lower than those of the control rats, but testicular content and basal plasma level of testosterone were not significantly changed. On the other hand, in vitamin E supplemented rats, FSH and LH content in pituitary tissue was significantly higher than that of the controls, but there was no significant rise in basal FSH and LH level in plasma. The testosterone level was significantly elevated in both testicular tissue and plasma. It was also demonstrated that basal plasma testosterone and F.T.I. were increased in normal male subjects following oral vitamin E administration and the responsiveness of plasma testosterone levels to HCG was significantly higher during vitamin E administration than before administration. These results suggest that vitamin E may play an important and potent role in hormone production in the pituitary-gonadal axis in humans and rats.

Remember, my PCT reccomendations don't exist in a vacuum; you seem to have taken one part and looked at it, then another, then another...but you need to really look at how the various parts interlock...because alone, each part is nothing special...but all together, I feel it's the optimal PCT.

[RhinoChaser48]

Thank you for taking the time to respond.

Originally Posted by hooker

Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-protocol of the 'Arimidex and tamoxifen alone or in combination' (ATAC) trial.

Hmmmmm.... I missed this one. I apologize.

Do you have evidence that exemstane does not interact with tamoxifen?

Any opinions on formestane or ATD?

Successfull? Maybe. Optimal? No.

I'm confused. Is your proposed goal complete suppression of estrogen/aromatase? Wouldn't that potentially cause health problems we normally aim to avoid? Or is this period of total suppression so brief that the potential health problems are a non-issue?



Now, the following abstract is not very clear with it's wording, but the significant impact vitamin E had in this study may be significant because it was a deficiency model. It might not be a deficiency model, but I don't know that without seeing the full text.

If you have a copy of the full text, would you mind emailing it to me?

Effect of vitamin E on function of pituitary-gonadal axis in male rats and human subjects.
The role of vitamin E in the endocrine system, in particular the pituitary-gonadal axis, was studied in humans and male rats by examining the hormonal differences between vitamin E deficient and supplemented conditions. In vitamin E deficient rats, pituitary content and basal plasma level of FSH and LH were significantly lower than those of the control rats, but testicular content and basal plasma level of testosterone were not significantly changed. On the other hand, in vitamin E supplemented rats, FSH and LH content in pituitary tissue was significantly higher than that of the controls, but there was no significant rise in basal FSH and LH level in plasma. The testosterone level was significantly elevated in both testicular tissue and plasma. It was also demonstrated that basal plasma testosterone and F.T.I. were increased in normal male subjects following oral vitamin E administration and the responsiveness of plasma testosterone levels to HCG was significantly higher during vitamin E administration than before administration. These results suggest that vitamin E may play an important and potent role in hormone production in the pituitary-gonadal axis in humans and rats.

I look forward to reading more of your articles, as well as your up-coming book. Thanks again.

[hooker]

Originally Posted by RhinoChaser48

Do you have evidence that exemstane does not interact with tamoxifen?

Reference #33.


I need to go to bed, I'll try to answer the rest of your questions tomorrown.

[RhinoChaser48]

Sweet, here it is:

J Steroid Biochem Mol Biol. 1993 Mar;44(4-6):677-80. Related Articles, Links


Inhibitory effect of combined treatment with the aromatase inhibitor exemestane and tamoxifen on DMBA-induced mammary tumors in rats.

Zaccheo T, Giudici D, Di Salle E.

Laboratory of Endocrinology, R and D, Farmitalia Carlo Erba, Milano, Italy.

The antitumor effect of exemestane (FCE 24304), an irreversible aromatase inhibitor, given alone or in combination with tamoxifen, was investigated in rats with 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors. The compounds were given once daily, 6 days a week for 4 weeks. Exemestane, given at the dose of 20 mg/kg/day s.c., induced 26% complete (CR) and 18% partial (PR) tumor regressions, compared to 0% CR and 6% PR observed in controls. Tamoxifen, given at 1 mg/kg/day p.o., induced 16% CR and 13% PR. The combined treatment caused 41% CR and 16% PR, thus resulting in a higher antitumor effect than either single treatment. The appearance of new tumors was reduced by each single treatment and almost totally prevented by the combined treatment. Serum prolactin (PRL) levels, assayed 4 h after the last dose, were unchanged in the group treated with the combination, whereas tamoxifen alone caused a slight increase of serum PRL. These results indicate that estrogen deprivation through aromatase inhibition and estrogen receptor antagonism causes a better inhibition of DMBA-induced mammary tumors than either treatment modality alone.

PMID: 8476783 [PubMed - indexed for MEDLINE]

[hooker]

Originally Posted by RhinoChaser48

Sweet, here it is:

It must have been mentioned in the full text but not the actual abstract.
Here's the one referenced in the text of the reference I used:

Clin Cancer Res. 2004 Mar 15;10(6):1943-8.Related Articles, Links

Pilot study evaluating the pharmacokinetics, pharmacodynamics, and safety of the combination of exemestane and tamoxifen.

Rivera E, Valero V, Francis D, Asnis AG, Schaaf LJ, Duncan B, Hortobagyi GN.

Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA. erivera@mdanderson.org

PURPOSE: We conducted a pilot study assessing the effects of the selective estrogen receptor modulator, tamoxifen, on the pharmacokinetics, pharmacodynamics, and safety of the steroidal, irreversible aromatase inhibitor (AI), exemestane, when the two were coadministered in postmenopausal women with metastatic breast cancer. EXPERIMENTAL DESIGN: Patients with documented or unknown hormone receptor sensitivity were eligible. Patients received oral exemestane at 25-mg once daily. Starting day 15, oral tamoxifen at 20-mg once daily, was added. We measured plasma concentrations of exemestane, estrone, estrone sulfate, and estradiol after 14 days of exemestane monotherapy and after approximately 4 weeks of combination therapy. The incidence and severity of adverse events were assessed by physical examination and patient reporting. RESULTS: We treated 18 patients. All had received prior chemotherapy and/or hormonal therapy, eight and six, respectively, with single-agent selective estrogen receptor modulators or irreversible aromatase inhibitors; no hormonal therapy was given within 30 days of study entry. Plasma exemestane concentrations and estrone, estrone sulfate, and estradiol suppression were unchanged after approximately 4 weeks of tamoxifen coadministration. All drug-related adverse events were grades 1 or 2; none was unexpected. Although not a formal study end point, antitumor activity was noted, with two partial responses and four cases of stable disease among 17 evaluable patients after a 9-month median follow-up (range, 2.5-19 months). CONCLUSIONS: This pilot study provides evidence that coadministration of tamoxifen does not affect exemestane pharmacokinetics or pharmacodynamics and that the combination is well-tolerated and active. Further clinical investigation is warranted.

[SWALE]

One thing we do need to always keep in mind is that we cannot reliably extrapolate studies conducted on females to draw draw conclusions on how males will respond hormonally.

Having said that, we also need to keep in mind we are just doing the best we can with what we have to work with. If you think there is a paucity of scientific studies to go by now, think of how it was way back in the early 80's when I first got interested in this stuff.

It is correct my HCG use is largely resticted to TRT application. However, IMPO, probably 250IU when used daily would be an upper limit for me. I would seek to avoid HPTA inhibition from the testosterone and the progesterone induced by the HCG. My use of HCG is merely to overcome the rate limiting step the recovery of the long-suppressed testes present.

But I must admit, it's great to be somewhere I am known as "safe and conservative"!