PCT: A Clinician's View Part II - Post Cycle Supplements, In Theory

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PCT: A Clinician's View Part II:
Post-Cycle Supplements - IN THEORY

- article originally published on-line December 30, 2005

Dana Houser, MD, MHSA, CISSN

Author's Note: If you have yet to visit the PRIMER and PART I of this series, please do so at the following addresses before proceeding.


Introduction

The three endogenous steroids of primary importance during the PCT time frame are testosterone, dihydrotestosterone, and estradiol as many “authorities” have likely kept you well informed. And it is true that from a quantitative standpoint, the most important androgen is in fact testosterone – BUT this should NOT detract in any way from the importance that is regaining control of the others. Without an understanding of exactly what is going on in your body, and why certain compounds help to correct the situation, choosing the right post cycle program can pose itself as quite the conundrum. This is namely due, in large part, to all the “wonder” recommendations floating about.

While your head has thrown into tail spin getting caught up on the various recommendations – reading any and every thing you can get your hands on, you feel you have arrived at the appropriate conclusion of what might be the very best post cycle options. But – we both know what you’re thinking! Have I made the right decision? Could I have read more? And, if you are like many I have seen in the past – is this the best subset of supplements/pharmaceutics to maintain my hard-earned newfound lumps and bumps?

During the planning stages of a cycle – you should entertain ALL options for appropriate post cycle. In fact, PCT and supplementation is something that should be considered a part of the cycle. Waiting until the end to make these vital decisions is likely flirting with disaster.

Unfortunately, there are some necessary digressions or necessary evils to have a complete understanding of before continuing on our journey – that is, as I let you in on this fact in our last discussion – welcome to Endocrinology 101. Oh yeah, if you struggle with particular points of the science discussion that follows – it is imperative to consider yourself in a place that would make AAS use an inappropriate consideration in the first place.

Endocrine Debriefing

In chemical terms, steroids are naturally occurring lipids, or fat-soluble substances. They all have similar chemical structures and are ultimately derived from cholesterol. Steroid hormones, aside from the male sex hormones, include estrogen, aldosterone, progesterone, cortisol, and even vitamin D. Cholesterol is modified by special enzymes in a series of steps to become all of the various hormones.

Normally, over 95% of testosterone is secreted by the testicular Leydig cells. In addition to testosterone, the testes secrete small amounts of the potent androgen dihydrotestosterone and the weak androgens dehydroepiandrosterone (DHEA) and androstenedione. The Leydig cells also secrete small quantities of estradiol, estrone, pregnenolone, progesterone, 17 alpha-hydroxypregnenolone, and 17 alpha-hydroxyprogesterone.

Dihydrotestosterone and estradiol are derived not only by direct secretion from the testes but also by conversion in peripheral tissues of androgen and estrogen precursors secreted by both the testes and the adrenals. Thus, about 80% of the circulating concentrations of these two steroids is derived from such peripheral conversion.


Summary of Relative Contributions (appx. %) of major steroid origins

Testosterone
Testicular Secretion: ~ 95%
Adrenal Secretion: ~ 1%
Peripheral Conversion of Precursors: ~ 4%

Dihydrotestosterone
Testicular Secretion: ~ 20%
Adrenal Secretion: ~ 1%
Peripheral Conversion of Precursors: ~ 79%

Estradiol
Testicular Secretion: ~ 20%
Adrenal Secretion: ~ 1%
Peripheral Conversion of Precursors: ~ 79%

Estrone
Testicular Secretion: ~ 2%
Adrenal Secretion: ~ 1%
Peripheral Conversion of Precursors: ~ 97%

DHEA-S
Testicular Secretion: ~ 10%
Adrenal Secretion: ~ 90%
Peripheral Conversion of Precursors: Not usually detected


In the blood, androgens and estrogens exist in either a free (unbound) state or bound to serum proteins. Although about 38% of testosterone is bound to albumin, the major binding protein is sex hormone-binding globulin (SHBG), which binds 60-80% of the testosterone (depending upon which source you get the figures from). This glycosylated dimeric protein is homologous to, yet distinct from, the androgen-binding protein secreted by the Sertoli cells. SHBG is synthesized in the liver, with the gene located on the short arm of chromosome 17. The serum concentrations of this protein are increased by estrogen, tamoxifen (discussed further in 2 parts), phenytoin, or thyroid hormone administration and by hyperthyroidism and cirrhosis and are decreased by exogenous androgens, glucocorticoids, or growth hormone and by hypothyroidism, acromegaly, and obesity. About 2% of the circulating testosterone is not bound to serum proteins and is able to enter cells and exert its metabolic effects. In addition, some of the protein-bound testosterone may dissociate from the protein and enter target tissues; thus the amount of bioavailable testosterone may be greater than just the amount of non-protein bound testosterone.


CONTROL OF TESTICULAR FUNCTION

I split this into the following two categories: Hypothalamic-Pituitary- <Leydig Cell / Seminiferous Tubule> Axis. From this point on, I will use the abbreviations HPLCA or HPSTA interchangeably with HPTA (more of a blanket term) – HOWEVER, we will get a BIT MORE SCIENTIFIC, because they are NOT the same and this mutual exclusivity certainly will pan out along this series!

Hypothalamic-Pituitary-Leydig Cell Axis (HPLCA)

The hypothalamus synthesizes a decapeptide, gonadotropin-releasing hormone (GnRH), and secretes it in PULSES every 90-120 minutes into the hypothalamo-hyphysial portal blood. After reaching the anterior pituitary, GnRH binds to the gonadotrophs and stimulates the release of both leutinizing hormone (LH) and, to a lesser extent, follicle-stimulating hormone (FSH) into the general circulation. LH is taken up by Leydig cells, where it binds to specific membrane receptors. The LH receptor is a G protein-coupled receptor containing seven transmembrane domains with a serine and threonine-rich cytoplasmic region containing a phosphorylation site and a 350- to 400-amino acid extracellular hormone-binding domain. The binding of LH to the receptor leads to activation of adenylyl cyclase and generation of cAMP and other messengers that ultimately result in the secretion of androgens. In turn the elevation of androgens INHIBITS the secretion of LH from the anterior PITUITARY through a direct action on the pituitary and an INHIBITORY effect on the HYPOTHALAMUS. Both the pituitary and hypothalamus have androgen receptors (more later). Experimentally, pure androgens such as DHT reduce LH pulse frequency, while estradiol reduces LH pulse amplitude. However, the major inhibitory effect of androgen on the hypothalamus appears to be mediated principally by estradiol, which may be derived locally through the aromatization of testosterone. Leydig cells also secrete small quantities of oxytocin, renin, corticotropin-releasing factor, inslin-like growth factor I (IGF-1), transforming growth factors alpha and beta, IL-1, lipotropin, beta-endorphin, dynorphin, angiotensin, inhibin, gastrin-releasing peptide, stem cell factor, substance P, and prostaglandins, which may be important for paracrine regulation of testicular function. These may be optimal future adjunctive targets.

Hypothalamic-Pituitary-Seminiferous Tubule (HPSTA)

After stimulation by GnRH, the gonadotrophs secrete FSH into the systemic circulation. This glycoprotein hormone binds to specific receptors in Sertoli cells and stimulates the production of androgen-binding protein. FSH is necessary for the initiation of spermatogenesis. However, full maturation of the spermatozoa appears to require not only an FSH effect but also testosterone. Indeed, the major action of FSH producing androgen-binding protein can be viewed as PURELY EVIL. I beg you not to look at it this way as it aids us to maintain high intratubular concentrations of testosterone (likely more an evolutionary effect for production of offspring in the realm of spermatogenesis, but the test concentration also has other advantages – we will discuss this in more detail later).

In addition to androgen-binding protein, the Sertoli cell secretes several other substances like LH does: GnRH-like peptide, IGF-1, transferrin, plasminogen activator (improtant side effect potential for steroid users), ceruloplasmin, mullerian duct inhibitory factor, H-Y antigen, and inhibin A and inhibin B. While I would love to talk about each of these factors as I find them fascinating future research items.

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PHARMACOLOGY OF AAS

AAS are a class of chemically related steroid hormones that promote both protein anabolism and masculinization. Chemically, they are analogues of testosterone. Pharmacologically, their dominant effect is net synthesis of protein in virtually all tissues that are capable of growth, including male reproductive tissue. Even effects that are commonly referred to as androgenic, for example, regulation of male sexual organs, can be considered to be anabolic; in fact, an androgenic effect has been described as an anabolic effect on sex organs (16).

Testosterone, other endogenous steroids, and hundreds of synthetic steroids fulfill this definition. The terms androgen and anabolic are OVERLY SIMPLISTIC and INADEQUATE, however, because some effects are not easily classified as anabolic or androgenic, and some are clearly neither (i.e. – decrease in SHBG). In fact, a remarkable feature of the AAS is their diverse and large number of effects. Virtually all tissues are affected in some manner, and often it is difficult to distinguish between primary and secondary effects. Further, individuals given the same dose sow a remarkable variability in response.

Despite intense research efforts (regardless of what many “authorities” suggest), NO steroid has been described that is purely anabolic OR androgenic. Furthermore, in healthy men, there is NO direct evidence for more than one receptor. Thus, the dual ability to promote growth and masculinize is inherent in the same molecule, therefore, the most appropriate designation remains anabolic androgenic steroid. Nevertheless, the term AAS is commonly shortened to “anabolic steroid” or “androgenic steroid” depending on the context. “Androgenic” is used for discussions that emphasize sexual differentiation, pubertal changes, virilization, and effects on primary and secondary organs of reproduction.


ANROGEN RECEPTOR

The notion of one receptor mediating androgenic effects in male reproductive tissue and another mediating anabolic effects in muscle tissue arose from the observation in experimental animals that some compounds exert anabolic activity and relatively little androgenic activity (17).

The hope of discovering an AAS devoid of androgenic activity fueled a concerted effort to synthesize and test new agents. Since nitrogen balance studies were cumbersome, a simple bioassay was developed that compared, in the same animal, the AAS-induced increases in weight of the prostate and of the levator ani muscle. The anabolic-androgenic ratio was interpreted as an index of relative dissociation of anabolic from androgenic activity. Although this assay did correlate reasonably well with nitrogen retention studies, the validity of the assay was later questioned. In addition, research on specific intracellular enzymes, differences in the affinity of compounds for receptor binding proteins, and differences in levels of receptors in various tissues showed that the diversity of responses could be explained by other mechanisms. Moreover, recent studies provide substantial evidence for only one receptor.

The androgen receptor has been isolated and characterized (18), and a cDNA that encodes the AR has been cloned and expressed numerous times during the ten years of research that brought us its characterization. Defects or single amino acid substitutions in the AR are associated with several diseases. Only one AR type has been discovered by either molecular biologic techniques or receptor-binding studies. The binding characteristics of receptors-isolated from reproductive tissue and from skeletal muscle are IDENTICAL (19). Antiandrogens also bind to the AR and compete with T and DHT for the binding sites. Perhaps the most convincing evidence for the one-receptor theory is research describing the clinical consequences of androgen receptor disorders and associated molecular biology of the androgen receptor gene (20).

Most of the effects of AASs are presumed to be mediated, like those of T in tissues that contain AR, which include reproductive organs, brain, kidney, liver, skin, skeletal muscle, cardiac muscle, bone, larynx, thymus, and hematopoietic and lipid tissue. You knew I would get to why all of this science stuff is important, especially considering PCT or even peri-cycle. Does anyone see the potential for side effects with the AR being expressed in all those endogenous tissues?

At the subcellular level, the effects are determined by the affinity, binding constant with the AR and molecular details of receptor DNA interaction, transcription, and translation. Within the target cell, the effects of AAS are presumed to be influenced by the same mechanisms that control the fate and effects of T. These include enzymes that activate and deactivate T, enzymes that control the activity of receptor androgen interactions, and differences in receptor content.


ABSORPTION, DISTRIBUTION, AND METABOLISM

None of the synthetic nonendogenous AASs have been studied as intensively as T. The synthetic agents are absorbed from the gastrointestinal tract, mucus membranes, skin, and intramuscular deposits. We have already discussed how most T circulates in the blood stream. It is important to note that the synthetic agents also have an affinity for SHBG.

The concentration of AASs and metabolites can be measured in serum and urine, and there are some data on concentration in serum relative to therapeutic effects; however, plasma levels are not commonly used to monitor dosing.

Free T diffuses into the cell where it may bind directly to the AR, undergo reduction of the C4-C5 double bond to 5-alpha-DHT by 5-alpha reductase, or be metabolized further. Both T and DHT bind to the same AR, although DHT is more tightly bound, leading to the hypothesis that we have all accepted as truth – DHT is the most active and potent intracellular androgen. Binding to the AR activates the complex, enabling it to interact specifically with DNA and activate specific genes. Some T is metabolized by aromatase to estradiol (actually still a bit more complex – see later), which binds to the estrogen receptor (ER). These important features of T metabolism emphasize that administration of T will result in a mixture of effects mediated by the T + AR and/or DHT + AR and estradiol + ER. In some cases, the effects at one receptor may be neutralized or enhanced by effects at the other.

The extent to which the effects of AASs are mediated at both ER and AR is less certain, in part because the metabolism of AASs has not been studied as extensively as that of T. Any synthetic AAS with a delta-4, 3-keto function is subject to metabolism by aromatase to the corresponding estrogens. A few estrogen metabolites of AASs have been described in humans, and in vitro studies indicate that many more are likely. Examples of AASs that are NOT substrates for aromatase are DHT, fluoxymesterone, mesterolone, and oxandrolone.

Receptor-binding studies confirm that ARs derived from muscle tissue or prostate tissue are the same, and that synthetic agents, T, and DHT bind to the same AR. All synthetic AASs undergo extensive metabolism primarily to hydroxylated and 5-alpha- and 5-beta-reduced metabolites. Most of these are excreted in the urine as sulfates or glucuronides. Various metabolites of synthetic AAS have been found in subcellular fractions of target tissues and their binding to AR has been characterized. Unlike T, however, 5-alpha-reduced metabolites of 17-alpha-methyl AASs are NOT more active than the parent compound (which likely dictates perceived differences in effectiveness between things classically considered AAS and those in the former/current PH/PS class).

Now, rationale guiding the basis for use of AAS by athletes likely centers on the fact that skeletal muscle tissue differs from other androgen-responsive tissues in that 5-alpha-reductase activity is low and T is present in greater amounts than DHT. Thus, T is the dominant intracellular agonist in muscle. In the experimental animal, the concentration of ARs varies markedly from one muscle group to another, and those with the higher concentrations respond the most to androgen (these effects are like adipocyte-alpha/beta receptor concentrations and what entirely OFFERS a complete model to understanding body composition – remarkably, many remain baffled – oh yeah, the authorities forget to tell you that you are STILL A SUBJECT OF YOUR GENETICS and without employment of REAL LIFE “TRICKS” with your usage, you are STILL GOING NOWHERE!!!). This parallels the observation that, in human males, the predominant response seen to anabolics remains that the back, chest, and upper arm are going to respond better than other muscle groups to AAS. HAS ANYONE THAT HAS USED ANABOLICS OF ANY VARIETY NOT EXPERIENCED THE BEST BODY COMPOSITION CHANGES IN THESE AREAS? I didn’t think so.


GLUCOCORTICOID RECEPTORS

Now, our discussion doesn’t end with the AR. One alternative hypothesis that does NOT require ARs is that AASs promote positive nitrogen balance and muscle growth by acting as an antagonist at glucocorticoid receptors (GRs), thereby inhibiting catabolic actions of glucocorticoids (20). This hypothesis is supported by studies in adrenalectomized-castrated animals (21) and by cell culture experiments showing that, in cells that express AR and GRs, oxandrolone suppresses glucocorticoid action via a novel type of cross-talk between the receptors (22).

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ONSET, DURATION, AND REVERSIBILITY OF
ADVERSE EFFECTS

The onset of hormone suppression may be very rapid. Methyltestosterone, 25 mg/day for 3 days followed by 240 mg/day for 3 more days led to highly significant declines in serum T, DHT, FSH, and LH. Three days after the 6 days of methyltestosterone, the levels of T and DHT were still low, while FSH and LH had returned to normal.

The hallmarks of reversibility are marked variability and unpredictability. Some effects in some individuals rapidly reverse and others very slowly IF AT ALL. At one extreme, diminished height resulting from premature closure of epiphyseal plates is completely irreversible, while elevated levels of ALT and AST rapidly reverse. Of course, I have pointed out that the premature closure of epiphyseal plates in my best efforts of thought would be attributed to increased estrogenic turnover via aromatase accounting for this discrepency when AAS are inappropriately come off of perhaps citing an even more imperative rationale for proper PCT.

Cholestatic jaundice and peliosis hepatis (both talked about at length later in this article) ARE usually reversible and to some extent, hepatic adenoma will regress with the discontinuation of AASs. Voice changes are particularly slow to change.

Most of the virilizing effects in females are considered irreversible, although detailed studies are NOT available. Changes in body composition take many months to subside fully provided inappropriate PCT – I am not a firm believer in the notion that NONE of the gains achieved on a cycle can be retained. After a 12-week course of T enanthate, body fat and LBM did NOT return to baseline for approximately 6 months and, after 1 year of ND, the forearm fat content remained low for AT LEAST another 6 months.

Hypogonadotrophic hypogonadism induced by AASs is reversible, although the rate of recovery may be quite slow and depends in part on the particular AAS that was used and the duration of use. For example, following a 2-week course of methandienone (30 mg/day), FSH and LH returned to baseline in 7 days, but T levels were still low after 2 weeks, whereas, after 12 weeks of fluoxymesterone (10-30 mg/day), plasma levels of T were back to normal in 1 to 2 weeks. The esters of nandralone and T produce the longest lasting effects. In contraception studies with T esters lasting several months, the sperm count may not return to normal for 20 to 30 weeks after drug discontinuation. Athletes taking high doses of N esters frequently experience azospermia, which may last for 20 weeks after drug discontinuation, and plasma levels of FSH, LH, HDL, cholesterol, and T take 20 to 50 weeks to recover. Occasionally, azospermia may still be present after 1 year without steroids. We will explore the topic of azospermia more in the pharmaceutic subset of this series.

Studies do but a couple things; they tell us that the degree of the hypogonadism is highly variable, and the severity may be extreme. The time to total recovery is correlated with some combination of the total dose, duration of treatment, and serum half-life of the agent. The ways in which this process of recovery may be expedited will be discussed in the remaining sections of this series. PLEASE DO NOT CONSIDER FULL EMPLOYEMENT OF THESE STRATEGIES UNTIL ALL REMAINING PARTS HAVE BEEN RELEASED AND OF COURSE, ONLY WITH THE GUIDANCE OF YOUR OWN EXAMINING PHYSICIAN OR THE INDIVIDUAL(S) ASSUMING THAT ROLE.
PHARMACOLOGY OF AAS

AAS are a class of chemically related steroid hormones that promote both protein anabolism and masculinization. Chemically, they are analogues of testosterone. Pharmacologically, their dominant effect is net synthesis of protein in virtually all tissues that are capable of growth, including male reproductive tissue. Even effects that are commonly referred to as androgenic, for example, regulation of male sexual organs, can be considered to be anabolic; in fact, an androgenic effect has been described as an anabolic effect on sex organs (16).

Testosterone, other endogenous steroids, and hundreds of synthetic steroids fulfill this definition. The terms androgen and anabolic are OVERLY SIMPLISTIC and INADEQUATE, however, because some effects are not easily classified as anabolic or androgenic, and some are clearly neither (i.e. – decrease in SHBG). In fact, a remarkable feature of the AAS is their diverse and large number of effects. Virtually all tissues are affected in some manner, and often it is difficult to distinguish between primary and secondary effects. Further, individuals given the same dose sow a remarkable variability in response.

Despite intense research efforts (regardless of what many “authorities” suggest), NO steroid has been described that is purely anabolic OR androgenic. Furthermore, in healthy men, there is NO direct evidence for more than one receptor. Thus, the dual ability to promote growth and masculinize is inherent in the same molecule, therefore, the most appropriate designation remains anabolic androgenic steroid. Nevertheless, the term AAS is commonly shortened to “anabolic steroid” or “androgenic steroid” depending on the context. “Androgenic” is used for discussions that emphasize sexual differentiation, pubertal changes, virilization, and effects on primary and secondary organs of reproduction.

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ANTI-ESTROGENICS

(1) Aromatase Inhibitors

The aromatase enzyme is the rate-limiting step in the conversion of androgens to estrogens. Aromatase is an enzyme complex containing a cytochrome P-450 hemoprotein and a flavoprotein, nicotinamide-adenine dinucleotide phosphate P-450 reductase. The cytochrome P-450 catalyzes a series of 3 hydroxylations of the androgen substrates androstenedione and testosterone. Because the aromatase cytochrome P-450 has little homology to other P-450 enzymes, it has been assigned to a separate gene family designated CYP19.

The aromatase enzyme selectively catalyzes only the production of estrogens, whereas other similar enzymes govern the production of other steroid hormones, including glucocorticoids, androgens, and mineralocorticoids. The optimal way to decrease estrogen production is to selectively target the aromatase enzyme without inhibiting the activity of the other enzyme systems.

Aromatase production sites in males include: adipose tissue, liver, muscle, placenta, and hair follicles. One problem with aromatase inhibition is that it is incomplete because increased estradiol synthesis signals the pituitary to correct this hormonal discrepency, increasing both FSH and LH secretion. FSH is a more direct stimulant of extra aromatase whereas LH stimulates androgenic substrate for the conversion. You are actually COMPOUNDING THE PROBLEM if you are not careful.

Aromatase inhibitors are of two general types: type I, referred to as suicide inhibitors (I am particularly adverse to this dubbing!), and type II equal competitive inhibitors.

Once a suicide inhibitor binds the aromatase enzyme, the sequence of hydroxylations is initiated, but the hydroxylations produce a covalent bond between the enzyme and the inhibitor that irreversibly blocks the activity of the enzyme. After exposure to a suicide inhibitor, aromatase enzyme can only be restored with new enzyme synthesis.

Competitive inhibitors reversibly bind to the active enzyme site, and either no enzyme activity is triggered or it has no effect. The inhibitor can dissociate from the binding site to allow renewed competition between the inhibitor and the substrate for binding to the active binding site. For the effect of a competitive inhibitor to persist, a constant concentration of the inhibitor IN EXCESS OF THE SUBSTRATE MUST BE PRESENT.

ZEE CURRENT CROP:
4-androstene- 3, 6, 17-trione / androst-4- ene-3,6,17-trione
1, 4-androstadiene - 3, 6, 17-dione
6, 17-keto-etiocholeve-3-ol tetrahydropyranol
3, 17-ketoetiochol-triene
3’, 5, 7-trihydroxy-4’-methoxyflavone
6-acetoxy-3-hydroxy-17-keto-etioallocholane
17a-methyl-17b-hydroxyl-3-keto-delta 1,4,6-etioallocholtriene
4-hydroxyandrostenedione

I wrestled up the various brands containing the ingredients listed above that fall under the umbrella of “anti-estrogenics,” in many cases, aromatase inhibitors. These compounds will be addressed throughout this series because they are the most often hyped and subsequently the most often sought after if a supplement is to be on board in the post cycle realm, sometimes at the expense (mistakenly so) of the basic latter supplements I endorse to follow.

(2) Estrogenic Channeling Agents

Indole-3-Carbinol

Only one kind of vegetable interferes with the estrogen pathway and that is a cruciferous vegetable. These get there name from the crosslike stem they all have in common, from broccoli to cauliflower. European women who ate more cabbage had lower breast cancer death rate. Cruciferous vegetables decreased the risk by 40 percent in a Wisconsin study. So, how do they work and why would I include this talk of female breast cancer in a study who’s primary target remains males in the post-cycle time frame?

The secret ingredient is called indole-3-carbinol, which channels the breakdown products of estrogen into far more “good” estrogen (2-hydroxyestrone) than “bad” estrogen (16-alpha-hydroxyestrone). As with good and bad cholesterol, you can increase or decrease either amount of estrogen. Indole-3-carbinol can double the amount of good estrogen while decreasing the bad, which the Journal of the National Cancer Institute reported to decrease the amount of “bad” estrogen thereby subsequently leading to a decrease in breast cancer in Finnish women studied.

The rationale for it being discussed here is one of pure origin, however, similar application can be applied to males in the post-cycle time frame. That is, a decrease in the “bad” cholesterol remains of utmost importance in both scenarios, while the potential consequence of its existence does not share any similarity.

While 1% of breast cancer is found in males, it is NOT breast cancer prevention that is found to be the largest benefit here. The shunting described above that suggests the favoring of 2-hydroxylation over 16-alpha-hydroxylation may reduce risk of clinically evident prostate cancer (12). This shunting has another effect: it aids the liver’s Phase I and Phase II enzymes allowing a bit more wear and tear from the cycle (especially encouraging news for the C17-alkylated oral users). Oh yeah, gentlemen there is this shunting effect that would also be beneficial in fat deposition or feminizing effects seen in the post cycle time frame.

We’ll explore some UNIQUE dosing parameters as well as absorption protocols for the most benefits of this extract.

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PRO-TESTOSTERONE

DHEA (dehydroepiandrosterone)

DHEA is a natural steroid hormone produced from cholesterol by the adrenal glands. Some bodybuilders use it for PCT because it is purported to get the libido back, and some studies suggest that it is effective in regenerating atrophied testicles. It is also said to give you a better sense of well being, restore natural test production, and is not suppressive. DHEA is subject to being aromatized in peripheral tissues to estradiol. This could be exponentially increased during the post cycle period.

When evaluating what may be appropriate for the post cycle period, the interjection of items at this point in the steroidogenesis pathway are done at an inopportune time. DHEA has the dual negative potential to first increase estrogens (there is nothing to say pathways will shunt as you desire them to) and second, to decrease HDL and this could not be a more inopportune time for this level to be even hypothetically affected by continued exogenous substances. Further discussion of this aspect will be seen through this series’ unfolding as well as below.

Cordyceps (Cordyceps sineus)

A handful of studies conducted in Chinese subjects have shown increases in libido and restoration of testosterone and DHEA levels (from low to normal) following cordyceps supplementation. In addition, using cordyceps as a way to normalize these suppressed DHEA levels can help modulate the cortisol : DHEA ratio within a lower (and healthier) range. Because more than 200 different species of the cordyceps mushroom exist, it is important to look for the one on which the majority of the research has been conducted: the Cs-4 strain (typically standardized for mannitol content as a marker compound).

Tribulus Terrestris

Here is an example of a supplement with quite the storied past. Tribulus terrestris has a long history of use in Eastern Europe and China as a liver tonic and natural hormone stimulator. It has also been used for sexual dysfunction and infertility. Western practitioners became aware of the Bulgarian pharmaceutical (Sopharma) product designated to treat hormonal insufficiency and a potential fertility therapy.

Tribestan is the trade name of a formula with tribulus and other herbs sold in Eastern Europe. After a strong underground following among bodybuilders brought it to the U.S., Sopharma licensed the formula to several American supplement companies for sale here. Company claims purport up to 30 percent testosterone increases in men and subsequent increased men’s libido, strength of erections, and sperm production. Though the purported studies that support these claims are still outstanding in presentation, the supplement’s cult following certainly raises an eyebrow.

The mechanism of action is purported to be increased secretion of LH from the pituitary. One thing warranting exploration is how tribulus does have a female-SPECIFIC stimulatation of FSH production. Again, this does not appear to be the case in males.

I have discussed at length in my Tribulus article some of the potential overlooked benefits, but I am going to step outside of that series here and report a link I see to another hormonal system that plays an important role in the post-cycle period. Tribulus terrestris provides a safe, non-hormonal stimulation of the endocrine system emphasizing testosterone AND estradiol (again, it is an LH stimulator) production and liver enhancement. The important point I want to make is that both of the aforementioned effects contribute to and augment the metabolic action of HGH and IGF-1 as both testosterone and estrogen increase their production.

Additionally, imperative effects of tribulus during the PCT time frame could be the improved libido production and increased sperm count noted. It also acts as a liver tonic that further contributes to better hormone production and phenomenal potential after C17-alkylated hormonal use. A little biochemistry recall: the liver synthesizes hormones from cholesterol and breaks down fats to EFAs, which also play major roles in hormone production.

One more positive. Tribulus boosts the break down of proteins to amino acids for the creation of new muscle cells, which directly impacts growth hormone. The more muscle you have, the more endogenous HGH the body will produce – and vice versa. The effect tribulus has on protein greatly complements the actions of growth hormone and creates better energy usage, exercise recovery, and stamina. For this reason, the herb offers significant benefits for professional athletes despite negative press.

From body composition studies that didn’t show instantaneous “results” – the herb found itself placed very far down the list of some bodybuilder’s arsenals. This is unfortunate because bodybuilding is a complete science (ok, so it may be my dream that all consider bodybuilding that, BUT THE HUMAN BODY VERY MUCH IS THE SCIENCE!!!)

It does not end there, the fruit and root of Tribulus terrestris also contain metabolites like phytosteroids, flavanoids, alkaloids, and glycosides. These bioactive compounds have a strong and beneficial effect on the immune, sexual, and reproductive systems. It also reduces cholesterol, helps to prevent kidney stones and has been reported to offer a sense of well being (more later on psychiatric effects of cycle and post-cycle use). One clinical study revealed it has the ability to dilate coronary arteries, making it an ideal heart tonic (STAY TUNED TO THIS ARTICLE FOR MORE HERE!)

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Chaste Berry (Vitex Agnus – Castus)

For menstrual cycle irregularities and PMS – yes.
For testosterone ... Ummmmm – N-E-X-T!

MEGA Minerals (Zinc/Magnesium)

Oftentimes, our being caught up in the marketing hype of “ZMA” formulas to increase testosterone levels is what misleads the consumer to thinking these minerals have no application. This could NOT be a bigger misconception, especially during the post-cycle time frame. We will address zinc and magnesium one by one.

Magnesium Glycinate (Patent #4,830,716)
According to recent Hanes and Gallop surveys, at least 72% of all adult Americans fall short of the U.S. RDA for magnesium (bodybuilders whose nutrient tallies increase precipitously are the worst offenders). Serum (blood) magnesium levels are NOT an accurate test for total body stores of this mineral because magnesium is primarily a cellular mineral. Also, stress depletes this mineral rapidly. During the post-cycle time frame, the body experiences a significant stress load with its newfound exogenous extraction and anabolic depletion. Thus, supplementing magnesium is of DIRE concern for individuals going through PCT.

Magnesium is a catalyst for at least 30 organic functions. Some of its benefits include: protein synthesis, regulation of parathyroid hormone release which regulates bone calcification, cellular respiration, nerve transmission, prostaglandin synthesis, and cardiac muscle health.

Some of the most alarming magnesium deficiency symptoms which are rarely diagnosed by the medical profession relate to the following disorders: hypotension, hypertension, kidney stones, muscular weakness, neuromuscular irritability, hemolytic anemia, bronchial asthma, organic brain syndrome, migraine headaches, tachycardia, cardiac arrhythmia, myocardial infarction, edema, hyperkinetic behavior, insomnia, severe muscle pain, seizures, vertigo, chronic fatigue syndrome, diabetes, coarse muscle tremors, osteoporosis, psychiatric disorders, shortness of breath, and poor pulmonary function.

Those that like the “you can get enough magnesium from diet alone” proponents are very far off! This is in addition to most supplemental magnesium coming in oxide, aspartate, sulfate, or hydrochloride forms which can cause diarrhea and abdominal cramps among sensitive individuals. This is further compounded by combining magnesium with other minerals – NAMELY calcium WHICH IMPEDES the absorption of magnesium in these forms, yet most formulas boast combos of these two vital minerals in some way, shape, or form. Magnesium glycinate, on the other hand, is a patented (U.S. Patent #4,830,716) revolutionary process of chelating magnesium to glycine so that magnesium is absorbed like an amino acid. It is so well absorbed that it is NOT dependent on stomach acid or diet. It is released easily into the target organs for higher absorption and nutrient density.

Zinc
An essential nutrient and a catalyst for over 30 bodily functions. Zinc deficiency plays a major role in the following health conditions: acne, anorexia nervosa, delayed sexual response, growth impairment, hair loss, fatigue, memory loss, macular degeneration, high LDL cholesterol,