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All About Testosterone..

Big-John

AnaSCI VET
Oct 25, 2012
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Found this at another board and thought it was a good read.



Learn everything you will ever need to know about testosterone and how it works. Find out the basics, how it reacts in the body, the difference between steroids and testosterone and much more...

By: Virtual Muscle Sep 10, 2003



From Rogue To Vogue

If you had asked a doctor 10 years ago about bumping testosterone into the high-normal range to enhance one's physique, chances are slim you would have gotten a positive response. "Testosterone is bad for you," he would probably say. "It will shrink your grapes to raisins, give you liver disease and make you backhand your Grandma!"

Enter 1996 and the legal availability of androstenedione (a-dione) and other prohormones. For the first time, "steroids" were legally available over the counter and testosterone became user-friendly. It could not only enhance strength and muscle size, but also improve body composition, bone density, libido, and immunocompetence. Some research even suggested T could make you smarter! Unfortunately, as supplement sales skyrocketed, so did marketing hyperbole. And so, too, did the bull about which company had the most potent prohormone concoction and how effective these "legal steroids" were.

If you are tired of being confused by "diones", "diols" and "19-nor" something-or-others - and want to know the real benefits and risks associated with testosterone boosting - read on. The information presented may just clear some of that fog in your noggin'.

The Basics

Testosterone is a 19-carbon steroid hormone produced primarily by the Leydig cells of the testes (in men) and the ovaries (in women). Smaller amounts are produced in the adrenal glands of both sexes. As a "steroid", testosterone belongs to the androgen class of hormones that also includes dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), androstenedione, and androstenediol. Six other classes of steroid hormones exist, including estrogens (the bane of male bodybuilders), progestins (some female contraceptives are made of these), mineralocorticoids (which help control water balance), glucocorticoids (mainly anti-inflammatory compounds), vitamin D, and bile acids.

In men, approximately seven mg of testosterone is produced each day, and blood levels range between 300 and 1000 ng/dL (10-28 nmol/L). Females, on the other hand, produce about 1/15th of this amount, leading to average blood levels of only 25 to 90 ng/dL (1-2.5 nmol/L). All steroid hormones are derived from the sterane ring structure, composed of three hexane (6 carbon) rings and one pentane (5 carbon) ring.


A-diol has the same ring structure as testosteron.

In healthy humans, the "rate-limiting" step in testosterone biosynthesis is the conversion of cholesterol into a hormone called pregnenolone. This hormone is then first converted to either DHEA or progesterone before being further degraded in a stepwise fashion to testosterone. Schematically, the two possible pathways look like this: (Enzymes have been omitted for clarity.)

Cholesterol » pregnenolone » progesterone » androstenedione» T
Cholesterol » pregnenolone » DHEA » androstenediol » T

After testosterone is secreted into the bloodstream, 96-98 percent is bound to proteins called albumin and globulin. This binding is thought to serve three purposes: 1) it makes testosterone soluble for transport within the blood, 2) it protects testosterone from degradation by the liver and kidneys, and 3) it serves as a reservoir or storage depot that can be used to dampen fluctuations in plasma testosterone.

The two to four percent not bound to plasma proteins is known as "free testosterone" and is thought to represent the biologically active fraction of the hormone; in other words, the amount that is capable of interacting with cells to cause physiological changes. And although recent data suggest this is most likely an oversimplification, we'll leave that discussion for another time.

Regulation of testosterone levels is governed by two factors: the total amount of testosterone in the blood, and the binding capacity of the plasma proteins. Obviously, as binding capacity goes up blood levels of free testosterone go down. Not surprisingly, certain drugs (anabolic-androgenic steroids, insulin, etc.) and perhaps nutritional supplements (like avena sativa, urtica dioica, etc.) can reduce the binding capacity of the blood and result in higher free-testosterone levels. [Editors' Note: Nutrition is also a factor in testosterone regulation; see our March discussion on this topic in Experiments vs. Experience.]

There is also mounting evidence that some types of pollution and pesticides can do the opposite. So much for running sprints in downtown Detroit! Also, testosterone production from the testes occurs the entire period of fetal development until about 10 weeks after birth. Then the gears screech to a stop until puberty - a time when men know all-too well their T levels are screaming.

This is a time when young men really blow past their female counterparts in body weight and muscularity - and get drawn toward sports like high school football, along with other aggressive pastimes. Sadly in many ways, testosterone levels begin to decline between the third and fourth decade of life. And by 80 (if we make it that long) we are only one-third the man we used to be, testosterone-wise.

The physiological actions of testosterone in males are far reaching. For example:

Growth of the penis, scrotum and testes during puberty
Enlargement of the larynx (voice box) that results in a deepening of the voice
Formation of functional sperm
Stimulation of hair growth - especially in the pubic area, chest, face, and, sometimes, the back
Increases in skin thickness and darkness
Increases in libido (sex drive)
Increases in basal (resting) metabolic rate
Increases in red blood cell number and total blood volume
Promotion of sodium and water retention in the kidneys
Increases in muscle protein synthesis resulting in increased muscle mass
Reductions in muscle glycogen breakdown during exercise
Increased calcium retention in bone
Decreased growth of hair on top of the head
Increased activity of the sebaceous (sweat) glands, sometimes resulting in acne
Promote a narrowing and strengthening of the pelvis

(Note: This list is meant to be illustrative rather than exhaustive. Testosterone has other effects on the body that are not listed.)

Of the "free" testosterone that interacts at the tissue level, much of it is converted within the cells to DHT - a more potent androgen - by the enzyme 5-alpha reductase. In the prostate, for example, this conversion is thought to be necessary for physiologic effects. Other tissues (like the epididymis, vas deferens, seminal vesicles, skeletal muscle, and bone) lack the 5-alpha reductase enzyme and therefore are thought to respond to testosterone directly.

The conversion of testosterone into estrogens (estriol, estrone and estradiol) is governed by the aromatase enzyme complex and occurs mainly in the liver, brain and fat tissue. Some bodybuilders attempt to avoid / reduce the conversion of testosterone to DHT or estrogens by maintaining low bodyfat and using drugs or nutritional supplements that block 5-alpha reductase and aromatase. Chrysin, saw palmetto and indole-3-carbinol are three examples of legal plant-derived supplements that may maximize testosterone levels by minimizing its conversion to DHT and estrogens. Unfortunately, the bio-availability of many "bioflavanoid" compounds when ingested is poor. Some cutting-edge supplement companies have trick "delivery systems" that attempt to address this problem.

It is important to recognize that blood levels of testosterone - all hormones for that matter - represent a dynamic balance between biosynthesis (which occurs in a pulsatile fashion) and biodegradation. As mentioned, the testes, adrenals and ovaries are responsible for testosterone biosynthesis, while the liver and kidneys are responsible for its biological degradation and excretion. So, for instance, increases in plasma testosterone commonly observed following a hard weight-training session are not just the result of increased production of testosterone from the testes, but also from a reduction in its clearance (blood flow to the liver and kidneys is reduced during exercise). Make sense?

This balance between synthesis and breakdown also make a single blood testosterone value extremely difficult to interpret. As noted decades ago, testosterone levels rise and fall throughout the day; therefore a single testosterone value could represent a peak or valley on the daily testosterone roller coaster.

Anabolic-Androgenic Steroids

So what is the difference between testosterone and anabolic-androgenic steroids (AAS)? Well, while testosterone is produced naturally in the body, AAS are synthetic analogs of testosterone that were first used medically in the US around the time My Three Sons and The Honeymooners were beaming with popularity.

By synthetic, I mean AAS are synthesized by guys in lab coats who, for most of their lives, have been taking science and chemistry courses. Several "relatively safe" AAS are used clinically to treat osteoporosis and muscle-wasting disorders. These are nandrolone decanoate (Deca Durabolin) and oxandrolone (Anavar), respectively. Examples of more potent, but potentially dangerous, AAS are fluoxymesterone (Halotestin), trenbolone acetate (Parabolan), methandrostenolone (Dianabol), and oxymetholone (Anadrol). In general, injectable steroids are more potent, safer and remain in the system longer than oral steroids. There are, however, a few exceptions.

Potential Side Effects From AAS Abuse

Though you may already be aware of potential side effects from testosterone abuse (note I said abuse and not use), here they are again: lowered HDL-cholesterol levels (good cholesterol), testicular atrophy, reductions in sperm count, prostate enlargement, liver damage (primarily with oral steroids that have been modified with a 17-alkyl substitution), menstrual irregularities, suppression of endogenous hormone levels (like LH and T), development of palpable breast tissue in men (also known as gynecomastia), clitoral enlargement, and acne.

Whether an individual using AAS will develop any of these side effects is difficult to predict because of the complex interaction between factors like drug type, dosage, duration of use, and individual (genetic) differences. Suffice to say there are safer ways to boost testosterone levels and gain an edge in the gym. More importantly, there are legal ways - at least for now.

The Good, The Bad & The Ugly (Of Andro Use)

Listen up! In case you've been Tae Bo-ing too much to notice, several US government agencies are attempting to have prohormones (andro) banned from over-the-counter sales. It seems to be only a matter of time; and androstenedione will most likely be the first to go. So while the apple's ripe, here is a myopic run down of the most effective testosterone precursors to pluck from the tree.

And make no mistake; I'm no "armchair physiologist". I have spent a considerable amount of time in the trenches collecting data on andro. To be exact, I've completed six separate university studies on various forms of prohormones, including androstenedione, androstenediol, cyclodextrin-complexed androstenediol, and a very popular androgen blend. So if visions of an andro-induced 30-pound weight gain - or a 400-pound bench press - are dancing in your head, you definitely need the information contained here.

In a nutshell, any andro product containing, primarily, "4" and "diol" somewhere in its name is probably your best purchase bet. For instance, although hopes were high when 4-androstenedione was first introduced to the market, its popularity faded quickly. In fact, anyone who still feels that 4-androstenedione is useful for testosterone boosting or muscle building in men should quit lifting and consider hawking abdominal rollers and cellulite creams. Granted, there may be effects in females (most companies have labels that advise females not to use), and perhaps there are yet-to-be uncovered effects on libido (sex drive). But in young, middle-aged - or older - males, 4-androstenedione is, essentially, worthless for muscle building. There, I said it. Sure, ingestion of 4-androstenedione can raise testosterone levels modestly (about 20-30 percent) at relatively high doses (300 mg or more), but the elevation in estrogens is greater. Like 2-5 times greater!

And, yes, you could use an anti-aromatase to minimize estrogen formation; but why bother? Especially when androstenedione's more potent cousin, 4-androstenediol, is still available. Both experimental and anecdotal evidence supports 4-diol's ability to raise testosterone levels and improve performance. And as long as a sublingual / transbuccal form of 4-diol is used, elevation in estrogens appear to be minimal. Currently, the most thoroughly studied supplement that contains 4-diol is Pinnacle's Androstat Popper.

As far as more expensive 19-nor prohormones go, much less is known about their effects, because they do not convert to testosterone, but, rather, to a weaker, related compound called nor-testosterone (nandrolone). In fact, one recent study showed that subjects who used a 19-nor combination product tested positive for nandrolone after only three days of supplementation. In addition, 19-nor-diol has a great reputation in gyms; especially with women trainers, because it does not promote water retention (unlike 4-diol).

Some friends who have used high doses of 19-nor-diol claim it wrecked their sex drive. But this has not been a universal observation. For all types of prohormones, though, forget swallowing unless you want to waste money and tax your internal organs unnecessarily. The recent development of cyclodextrin complexation, liposomes and bioadhesive tablets make oral administration pale in comparison.

Some companies have even developed nifty prohormone sprays. However, like most forms of andro on the market, hard data on the product's bioavailability in humans is non-existent. Besides, unlike pills, capsules and tablets, spray-on applications are not considered dietary supplements, and therefore aren't protected by the 1994 Dietary Supplement Health and Education Act (DSHEA), and will likely be caught in the cross-hairs when the feds wake up. Admittedly, sprays may have a more favorable pharmacokinetic profile for inducing anabolic gains; however this needs to be demonstrated in product-specific, university research.

Androgen Use In Women

Until recently few scientists have considered the potentially beneficial role that androgens may have in women. However, don't get too excited, girls. This comment applies largely to peri- or postmenopausal women. The production of androstenedione, DHEA and testosterone decreases sharply in some women during this time.

In clinical trials, women who received combined estrogen-androgen therapy noted increases in bone density, energy levels, well being, and libido, over and above those who received estrogen alone. Unfortunately, adverse effects like hair growth and increased cholesterol levels were also noted in some women. These effects, however, were both dose-dependent (the more androgens the women took the worse the side effects) and related to the mode of administration (swallowing being the worst; injections and implanted pellets being the best).

Would these same positive (and negative) effects occur from prohormone administration? No one knows. But it is not out of the realm of possibilities. While I certainly do not recommend prohormone use in pre-menopausal women, let's face it; it's already happening. And many women love the effects observed with relatively low doses.

Wrapping It Up

For current and future prohormone dabblers, consider the following:

Teens and trainees with less than several years of experience have absolutely no reason to use prohormones. Whether you like hearing it our not, the gains from proper training and diet will overshadow those from any legal supplement. Period.

Before considering the use of prohormones, educate yourself. Read about androgens, preferably from peer-reviewed scientific sources like textbooks and research articles. When hard data are unavailable, or the writing is over your head, be wary of summaries by self-proclaimed experts or "gurus". Consult with individuals who have both academic and practical experience in physiology, supplementation and training. In other words, look for guys / gals who can "talk the talk" and "walk the walk".

Avoid swallowing prohormones. The extra cost of cyclodextrin complexation and other legitimate forms of administration is well worth it.

Start with low dosages to discover your tolerance to side effects. Many women trainees start with 50-100 mg per day, while men use 100-200 mg per day. (If you are using a cyclodextrin complexed product divide these values by a factor of two).

Use prohormones for short periods of time (2-4 weeks), and then double the "off" time (4-8 weeks). Some athletes use tribulus terrestris during these off periods to coax their body's testosterone production back to normal. Typical dosages are 750-1500 mg per day. However, be sure to look for a product that contains protodioscin, the most anabolic of all saponins.

Have routine blood work done to determine your internal sensitivity to side effects (i.e. potential changes in cholesterol levels and liver function).

Although mild acne is no cause for concern (a sign that your body is producing more T), if you notice other more serious side effects, discontinue use immediately.

If minimizing side effects is an absolute must, stick with lower dosages of 4-diol and 19-nor-diol compounds. Based on data currently available, these appear to cause fewer side effects.

If you are a competitive athlete, don't use prohormones at all! Androstenedione and its cousins - including the 19-nors - are banned by most athletic organizations. Ignorance will not get you off the hook.

Don't expect miracles. Andro-induced gains in strength and size vary from person to person, but are typically modest. Put another way, even if you have every aspect of your program dialed in (training, diet, rest, and supplementation), the addition of a quality prohormone supplement will not have you benching 300 pounds if you currently struggle under 225.

There you have it, a quick but accurate treatise on prohormones. Make no mistake. Prohormones are steroids, although in comparison to classic (synthetic) anabolic / androgenic steroids, their effects are much, much weaker. And despite the media hype, no one is gaining 30 pounds of lean mass, or hitting 70 home runs a year, just by using andro.

As with any supplement, there are risks and benefits that should be carefully weighed prior to use. But as VM has said a hundred times: An informed decision is always better than an ignorant one. Now where is my bottle of Andro