Old stuff by Dr Marianco, good reads for anyone new
- 03-05-2007, 03:40 AM
Old stuff by Dr Marianco, good reads for anyone new
Low SHBG and Estradiol by Dr. Marianco.
The most common cause of low SHBG is excessive insulin - i.e. insulin resistance. Insulin resistance in turn leads to a cascade of events which results other hormone imbalances such as low testosterone production, suboptimal thyroid hormone activity, adrenal fatigue, etc.
Factors which together in a balance determine SHBG are:
1. Anabolic hormones generally reduce SHBG. These include testosterone, DHEA, insulin, DHT, and growth hormone.
2. Thyroid hormone, Estrogens, and Progesterone (by increasing estrogen receptors/sensitivity), increase SHBG.
In the absence of insulin resistance, the most common other cause of low SHBG is a very high level of other anabolic hormones - most frequency high testosterone from TRT. Those who use anabolic steroids at high doses often drive their SHBG to near zero.
When total testosterone is between 650 to 1000 ng/dl, and a person still has zero sex drive, I would look for other causes for sexual dysfunction - e.g. other hormone, neurotransmitter, or immune system problems.
Raising SHBG does not necessarily increase the risk for Alzheimer's disease. It is important to keep in mind the factors which lead to the risk of Alzheimer's disease.
Insulin resistance (i.e. excessive insulin levels) causes low SHBG. It also greatly increases the risk of Alzheimer's disease because it results in a higher level of inflammatory cytokine production (Cytokines are the chemical messengers of the immune system). It is the inflammation which is one of the underlying factors which leads to Alzheimer's disease.
SHBG level is most often a signal of the overall status of multiple hormone levels. The balance may give an indication of whether one is in an pro-inflammatory state or anti-inflammatory state - with inflammation leading to disease such as Alzheimer's disease, heart disease, strokes, cancer, etc. Some hormones such as some estrogens and insulin can lead to inflammation leading to illness. And other hormones such as the androgens (except DHT), growth hormone, and thyroid hormone, can lead to an antiinflammatory state, reducing the risk for illness. The balance determines the person's risk for illness.
What estradiol level is best for any individual often needs to be determined by trial and error. It is unique for each individual. Most do best around 30 pg/ml. But some do best at lower and higher levels. For example, I have a 65 y.o. patient with a total testosterone of 840 ng/dl and an estradiol of 47 pg/ml. He's having the time of his life - able to make love numerous times each night - after more than a decade of having no sex. The estradiol level works for him without side effects. Some may do better with much loser levels of estradiol - the response is highly individualistic.
Even with low SHBG - which is difficult to correct since it depends on the balance of so many hormones - when the other hormones and neurotransmitters are optimized, sex drive and the ability to have an erection can often return.
When total testosterone is supraphysiologic - i.e. over 1000 ng/dl - problems with libido and erections may occur. Testosterone increases dopamine in the brain in order to increase sex drive, reduce depression, give pleasure to activities. The problem is that dopamine is a very fragile neurotransmitter/hormone in its effects. Too high a dopamine level can cause tolerance to dopamine. This is similar to how one can develop tolerance to drugs such as cocaine and amphetamines which increase dopamine levels in the brain to cause their high. This can lead to the loss of libido when high testosterone levels are maintained for long periods of time.
Conversely, when one is deprived of testosterone (and hence dopamine) for long periods of time due to hypogonadism, one can get a high during the first few weeks of testosterone treatment since the brain becomes supersensitive to dopamine when it has been deprived of it (e.g. making more dopamine receptors to pick up the weaker dopamine signals). Unfortunately, as the brain then gets use to the higher dopamine levels, it will develop some tolerance, and libido will drop off - though we often wish that hopefully a good amount remains.
Free Testosterone will be determined by how much albumin is present to bind to testosterone (weakly bound testosterone), and how much SHBG is present to bind to testosterone (strongly bound testosterone). Albumin production is fairly stable and difficult to change without severe illness present. The albumin concentration is primarily determined by hydration - with dehydration increasing its level. SHBG is modified by multiple hormones: increased by thyroid, estrogens, progesterone; lowered by testosterone, DHT, DHEA, growth hormone, insulin; and is modified up or down by some medications, etc.
Is Free Testosterone a good measure of testosterone activity to determine whether nor not to adjust the testosterone dose? Not really.
First, Free Testosterone not a reliable test.
Secondly, and more importantly, it is also determined by multiple factors. It is more a measure of the sum of these factors than of testosterone activity itself.
For example, if there is too much estrogen, free testosterone can be lower since SHBG will be higher. If there is too little thyroid hormone, free testosterone can be higher. If there is insulin resistance (i.e. too much insulin), free testosterone will be higher. And so on. Thus, what is being measured by free testosterone? Certainly much more than testosterone activity itself. Therefore, it is difficult to say determine what needs to be adjusted to optimize function if free testosterone is used as the primary measure.
If anything, high or low free testosterone indicates there is a good chance that other hormonal imbalances (besides testosterone) are also occurring which need to be assessed and addressed - e.g. hypothyroidism, insulin resistance, high estradiol levels, etc.
Testosterone activity is determined by the sum of free testosterone's activity, weakly bound testosterone's activity (which has partial activity), and SHBG- bound testosterone activity (testosterone has signaling activity to SHBG receptors when bound to SHBG). Thus, Total testosterone comes closest to describing testosterone activity for clinical decision-making purposes for testosterone dosing.
One can also add DHT's activity (as some practitioners do) but one has to be careful since DHT can counteract testosterone's activity when DHT is too high.
How can one decide that the testosterone dose is too high or too low?
Using total testosterone, the TRT decisions become very simple:
1. The goal of TRT is getting the average total testosterone to at least 650 ng/dl (midrange on a reference scale from 300-1000 ng/dl).
2. If any problems remain, then it is due to other neurotransmitter/hormone/cytokine imbalances or excessive testosterone dose (i.e. supraphysiologic total testosterone).
These two constitute a rule of thumb - determined by the individual patient's circumstance - some patients need a lower, some patients need a higher dose of testosterone. However, no matter what the dose, realize that other imbalances in the body's information processing system (i.e. the sum of the nervous system, endocrine system, and immune system activities) may be present and need to be addressed.
Whether the total testosterone level over time is flat (as with pellets and usually alcohol-based gels) or with peaks or valleys (e.g. with testosterone injections, oil-based creams) is determined by the route of administration and the person's half-life for testosterone (and the ester if injections are used). Whether a flat or peak/valley testosterone time-curve is preferred depends on what a person best responds to.
Given how large an overlap there is between the symptoms of testosterone deficiency, thyroid hormone deficiency, cortisol deficiency, insulin resistance/diabetes, etc., it is important to look at the other hormones for a solution if total testosterone is at a good level.
How much estradiol (E2) is made depends a lot on how high total testosterone becomes and how much aromatase activity is present.
HCG use increases the production of aromatase - increasing estradiol production.
High testosterone doses (such as injections given once every two weeks), results in long-lasting supraphysiologic levels of estradiol. A solution in this case is to use smaller and more frequent doses of testosterone (such as by going to a twice a week injection - rather than larger once a week or once every two week injections). The lower peak testosterone levels resulting from more frequent injections reduces the exposure to aromatase, resulting in smaller estradiol levels. At the extreme, testosterone pellets usually have the least problems with estradiol. Of course, using Arimidex can also reduce estradiol.
- 03-05-2007, 10:25 AM
2. Post link to that post
3. Keep posting this type of refreshers
4. I am in particular interested at final recomendations to a patient on estrogen/DHT/enlarged prostate management
5. Dr John and Dr Marianco's posts
6. Use this thread, if it became loaded with good info it may became sticky
03-05-2007, 10:34 PM
He's not an MD, but good stuff nonetheless from Ksman :
Needle size: Large needles can core the rubber and you do not want rubber in your muscles. A shorter needle will have less flow resistance than a longer one. So a 1" #25 syringe might flow as well as a 1.5" 23?22 gauge. One can inject test cyp in small amounts with #29 .5" insulin syringes; the small pistons of a .5 ml syringe develops high forces that make injection times reasonable. Time to fill the syringe is extended.
Injection force: If you are having to push hard to get flow, it should not matter and should not create discomfort at all. You hand should absorb all of the forces involved. Do not push on the needle plunger with your injection site providing the opposing force. The plunger force required also depends on the diameter of the piston. Smaller pistons create larger pressures. So use a smaller capacity syringe if you can. For the glut's when self injecting with one hand, a 3ml syringe, while way larger than one needs for TRT doses, may be easier to handle... mostly from the point if view of one handed aspiration.
Injection site: All of the injected dose gets absorbed and it does not matter if glut's or vastus lateralis. Yes the glut's are more difficult for some and more time consuming. Injecting in the vastus lateralis is simply easier and you can visualize and avoid veins as well. When you read that someone started injecting in the glut's for a few weeks and then switched to the vastus lateralis and then really got a strong T effect, that is the delayed effect of starting TRT and would have occurred if injections had continued in the glut's. Note that the injection site in the glut's is very important to avoid major nerves and blood vessels. You need know how to landmark things properly.
Soreness: If the muscle injected is tight or tense, the result will not be good. For the glut's, massage and feel for any tight muscles (quite common). If you feel such, then the results can be unpleasant. The resulting pain can last for days and refer down the leg etc. If you massage the tight muscles and get them supple, then the injections can be painless. The upper leg can be quite insensitive to the needle penetrating the skin. Veins can hurt when punctured.
Bleeding and bruising: With the legs and lower fat, you can see the larger veins and the smaller surface veins. You can't see much of anything on your glut's. When you get used to injecting, you will notice that when you bleed and bruise, that this is also distinctly painful. That pain also is spread out and does not seem to refer to the point of injection like the skin prick does. When you go through a larger vein, two punctures, there can be a lot of blood. Apply firm pressure to stop bleeding for a while. A good injection can be totally blood free, at least with smaller needles (larger gauge numbers).
Injection site preparation: Other than the proper swabbing; one needs to carefully choose the site. In the glut's, to land mark you have to touch the area so it must be swabbed after that and then you can't see the location and need to start over... but you can't touch the swabbed area. Find a piece of larger plastic tube, 3/8" would be ideal, or a plastic pen top. Select the location and press on the skin to mark it. Then swab that location, and the target is clearly in view when you inject. This is particularly useful if for glut's you are standing and using a mirror to landmark, then lay down to inject.
Injection depth/needle length: For divided doses, the injected amounts can be quite tiny. For such small amounts, the depth into the muscle need not be very deep. For glut's, 1.5" is needed to get through the fat. For vastus lateralis; the skin and fat can be quite thin and 1" will be fine for larger doses and .5" will be fine for smaller doses.
Injection rate: This is mostly a concern for the larger doses. For smaller vastus lateralis doses, if a small (larger gauge number) is used, the flow rates will be automatically be slower from the gauge restriction and then there is no issue.
Massage: For larger doses, this may cause more damage as the pocket of fluid is forced around causing more tissue separation.
Heating the testosterone: Warm oil will flow better than cold. The temperature should not be an issue from a muscle trauma point of view. I can't see that this makes any difference other than the force required on the plunger and time to inject. Room temperature oil might be better to limit the flow rate for larger doses where fast rates can be painful. Test cyp is cotton seed oil based and test eth is sesame oil. I cannot recall which has the greater flow resistance. If you are happier warming the injection, no problem. Just don't assume that this is needed.
Injection frequency: When test cyp and such drugs were first approved, the product use guidelines were then approved and cannot be easily changed from a regulatory point of view. So these are carved in stone and do not reflect current best practices. So injecting every two or three weeks is totally insane. The T levels after the injection will cause higher levels of E and SHBG. The dropping T levels are unnatural and will leave you feeling crappy. Even injecting once a week is not good enough. If you have been doing so and feel drained and worse for a few days... you know. Inject more often... what works best for you is best. Blood work and your doc are not authoritative on how you feel.
Blood work: Blood work should be done 1/2 way through your injection cycle. If on a 3 week cycle, no meaningful results can be had at all.
Half-life of test: This is around 8 days for the larger doses that were used in the original studies; which were high to go with 2 or 3 week injections at the doctor's office. For 100mg weekly doses, the half-life will be shorter... and you will feel the drop off. When you see a reference to something like 14 days; that is not the half-life, but the time when the T levels drop back to baseline and the increase in T is no longer detectable. In continued dosing, as a dose wears off with weekly or longer injections; the levels can drop to levels that are lower than when you started TRT as the HPTA has shut down. So you can feel lower and worse off then when you started TRT... waiting for your next injection. And as the high T levels from these larger doses for longer injection cycles can trigger greater amounts of aromatization of T-->E, the E starts to interfere with T receptors which makes test less effective and reduces libido after a while.
Transient effects: The first few injections might not seem to do too much. Then there comes a few weeks of hyper sexuality as the body starts to respond to the higher levels of free testosterone. Then the body also ramps up SHBG which reduces the free T and T--E atomization increases. The resulting E competes with T at the T receptors which interferes with the action of the T. Libido then goes down and for some, libido and ED issues are worse than when they started TRT. This short term increase in sexually that then goes away is a very cruel event. You see what you can have then it gets taken away.
HCG & Sore and shrinking testicles: An effective TRT dose will shut down LH production and the testes will stop doing what they are designed to do. They will shrink and this causes soreness/pain for some. For young guys who need TRT, this also threatens fertility; but should not be depended on as a form of birth control. HCG, a female hormone of pregnancy, is almost the same as LH and has the same effects when men take it. It will keep the testes working. It is a protein structure, otherwise referred to as a peptide hormone. As such, it is in water and must be kept refrigerated when reconstituted. You would need the multidose vials, typically 10,000 IU. Do not get glass ampules! Inject with an insulin syringe into belly fat. IM injection is not needed, so spare the muscles from unneeded scarring. Research published in early 2005, which most docs are not aware of, showed that 250iu EOD of HCG injected SQ, not IM, maintained baseline testicular function in 'normal men' who has LH suppressed with T injections. Older men, 70's and older, may not be responding to their own LH and will not respond to HCG either. When you take HCG, any T that the testes produces will be added to the amounts injected. Docs have not had research based rational for dosing before, and practice has been to inject once or twice a week on the days before the injection. Do not use high doses of HCG, as this will cause the testes to down regulate the LH receptors. When you read about high doses, these are simply wrong or otherwise not applicable to continued use in TRT. When you mix HCG power with water, inject the water into the vial slowly down the side of the vial and swirl gently to mix - never shake. Load and inject slowly. These are the cautions for HGH which is also a peptide hormone. As water flows so well, it take care to keep flow rates slow through the needles.
Scrotum: Also see above section. When TRT shuts down LH production and the testes shut down; the scrotum also reacts and pulls up tight to the body in a manner similar to a prepubescent boy's. When HCG is administered, the scrotum will hang down the way that it should. This action of the scrotum pulling up to the body is a very obvious indicator that there is little or no LH.
Anti-E: Anti estrogens reduce the amounts of T that are automatized to E, which lowers E levels. Increased E will reduce the effects of T, kill libido and can cause breast tissue growth AKA gyno. The most well known anti-E is perhaps arimidex AKA adex or dex. The generic name is anastrozole. As a drug in tablet form, it is very expensive, costing $8-$10 per 1mg tablet. There are other products. You do not want to reduce E to extremes as that will also kill libido. High levels of T from large dose injections for longer cycles will cause higher amounts of T-->E conversion. Transdermals are also known to have higher conversion rates. If you are on TRT for a while and getting into high range on blood tests, you should be getting lots of nocturnal erections or wood. If you do not get morning wood, the problem can be levels of E that are too high for you. Blood work readings do not tell you much. Then if you take arimidex, perhaps the typical 1mg/week in 1/2 tablet divided doses, morning wood should happen. Along with that, libido should increase and ED problems reduced if your blood vessels are healthy. So let your morning wood be your guide to determine if T:E ratios are ok. You will have had morning wood during the early parts of your TRT when you also had the hypersexuallity. The morning wood goes away over time. Some docs/clinics will start anti-E at the start of TRT.
HCG+T: If you are injecting both and the HCG is EOD, then you can also inject your T on the same day. So for 100mg/wk of test T, you can inject 28mg of test EOD (which would be 0.14ml for a 200mg/ml compound). 0.5" #29 .5ml insulin syringes can be used for both. When drawing up test cyp/eth into these syringes, the preservative alcohol will boil or 'flash' as it hits the vacuum in the syringe. This boiling stops as the vapor pressure of the alcohol balanced in the syringe and the vapor will reincorporate with the fluid. That does take time. Injecting takes about 10-14 seconds for 0.14ml. The small piston of the 0.5ml syringe creates very high pressures.
Building muscle mass and loosing fat: This should be easy with a high normal range of total T. I will not get into wieght training etc. Just note that you need protein to build muscle. If you start to work out and start to gain some muscle, and start to feel persistant hunger between your normal meal patterns; this is your muscles talking to you. Don't eat carbs to curb that hunger, you probably have enough carbs in your diet. Get a whey protein power 'shake mix'. These are inexpensive in large formats at Sam's Club and Costco. Otherwise can be found in some pharmacies, GNC and WalMart. Do not use a meal replacement product such as slim-fast. Look for around 22-23 grams of protien per serving which is usually a 60ml scoop. You might want to use two scoops per serving. As you gain muscle, that muscle mass uses carbs 24x7. So gained muscle helps you loose fat.
Cholesterol: Often an effective TRT dose will also lower low density cholesterol while keeping high density cholesterol the same or slightly increasing it. Triglicerides can also be lowered. Some progressive docs will use TRT as an cholesterol lowering therapy. One can avoid statin drugs in some cases.
Costs: Insurance may cover injectables or refuse to pay for any injectables. Test cyp and eth are very cheap compared to transdermals. Some insurance will pay for the expensive transdermals and refuse to pay for the less costly injectables. 10ml of test cyp (20omg/ml) at Walgreen's seems to be going for $99 for a generic. The same generic can be had for $42 at Sam's Club with a business membership. So for some without insurance, injectables can be cheap... it is the doctor consults and blood work that makes TRT costly. Buy syringes in boxes of 100. At Sam's 1.5" #23 3ml syringes are $18/100. Walgreen's will ten in a bag for you and charge more than $1.00 each.
How do you feel?: Mood should increase with TRT and many also report improvements when HCG is used after been on TRT. Same with anti-E. But if HCG and/or anti-E starts when TRT is started, one would not notice independent effects. It one has been low on T for a long time, there long term effects will have created changes in brain function that will take longer to resolve, part of that been habit of thought process etc. Many men with low T are also depressed and that an other life circumstances may also contribute. Vitamin T can do wonders. With its boost, get motivated to improve your diet, build some muscle mass and try to take some actions to improve external factors that affect how you feel about life. You may find that as you start to feel better on T, that the negative effects of alcohol are more noticeable. Listen to your body. Alcohol is also thought to increase aromatization as well. T should allow you to be better able to judge what your body wants and dislikes. And if you smoke... stop.
03-05-2007, 10:38 PM
And Dr John!
We have already learned a practical bit about the various hormones that make up the metabolic “symphony” which comprises our hormonal milieu. We know where these hormones are produced, what modulates their production, and the target tissues of their various and varied actions. But we still need to integrate this knowledge into a practical “recipe”, if you will, so the clinician may return to his/her practice, and immediately begin screening for, and successfully treating, male hypogonadism. In other words, how do you actually administer Testosterone Replacement Therapy for men?
Should EVERY adult male patient who presents at your office be automatically screened for hypogonadism? About half of all men over the age of fifty are in fact hypogonadal (when tested for Bioavailable testosterone—more on that later). Certainly the answers to Medical History will lead the way toward suspicion of same, yet the complaints related to this insidious condition are sensitive without being specific. Clinical suspicion is further clouded because there is no way to correlate either the number of individual complaints, or the relative magnitude of each, to the severity of the hypogonadotrophic state on laboratory assay. The number one complaint which should hoist the proverbial red flag is Erectile Dysfunction. This is also the symptom of hypogonadism which, aside from all the seriously deleterious effects of same (cardiovascular disease, diabetes, osteoporosis, increased risk of cancer, depression, dementia, etc.), is most likely to bring the patient to actively seek TRT—and to remain compliant in your treatment regimen.
Following a good Medical History, which laboratory assays should be run as part of your initial hypogonadism workup? Following is my list, but certainly other specialists in this area run expanded or attenuated panels, per their experience and expertise. Of note, there are several other tests which should be included to complete the true comprehensive Anti-Aging Medicine workup (i.e. homocysteine, fasting insulin, comprehensive thyroid study, etc.), as this chapter is concerned solely with administering TRT. And as always, the panel is tailored to the individual patient. Here they are:
· Total Testosterone
· Bioavailable Testosterone (AKA “Free and Loosely Bound”)
· Free Testosterone (if Bioavailable T is unavailable)
· Estradiol (specify “ultrasensitive” assay for males)
· Thyroid Panel
· Comprehensive Metabolic Panel
· Lipid Profile
· PSA (if over 40)
· IGF-1 (if HGH therapy is being considered)
Two weeks after initiating a transdermal, or five weeks after the first IM injection:
· Total Testosterone
· Bioavailable Testosterone
· Free Testosterone (if Bioavailable T is still unavailable)
· Estradiol (specify the Extraction Method, or “sensitive” assay for males)
· DHT (especially if patient is using a transdermal delivery system)
· FSH (3rd Generation—ultrasensitive assay this time)
· Comprehensive Metabolic Panel
· Lipid Profile
· PSA (for more senior patients)
· IGF-1 (if GH Therapy has been initiated already)
INDIVIDUAL ASSAYS EXPLAINED
This is the assay your patients will most focus on. It’s also the one physicians who do not understand TRT will use to deny patients the testosterone supplementation they want, and need, when Total T is at low-normal levels. Total T is important for titration of dosing, but its relevance is reduced in older men (by virtue of their increased serum concentrations of SHBG), in favor of:
Where we actually get the “bang” for the hormonal buck, so to speak. This is the actual amount the body has available for use, as the concentration of hormone available within the capillary beds approximates the sum of the Free Testosterone plus that which is loosely bound to carrier proteins, primarily albumin. If Bio T is not readily available, Free T may be a second choice substitute, as Bio T and Free T serum concentrations are well correlated.
This assay is especially important to draw, up-front and at follow-up, if a transdermal testosterone delivery system is preferred by the patient. I’ll explain why later. DHT level may also help indicate cause for ED symptoms.
There are several reasons why this assay is VERY important, and should not be ignored in ANY hypogonadism work-up (or subsequent regimen). First, you definitely need to draw a baseline. Next, elevated estrogen can, in and of itself, explain hypogonadal symptoms. If E is elevated, controlling serum concentrations (usually with an aromatase inhibitor, which prevents conversion of T into E) may suffice in clearing the symptoms of hypogonadism. And finally, rechecking it after beginning the initial dose of testosterone will give the astute physician valuable information as to how the patient’s individual hormonal system functions, as well as making sure estrogen does not elevate inappropriately secondary to the testosterone supplementation.
I don’t waste time and money drawing estrone and estriol. E2 is the player of interest here. Unless you specify a ‘sensitive’ assay for male patients, the lab will run the Rapid Estradiol for fertility studies in females, which is useless for our purpose here. Quest Diagnostics calls this their Estradiol by Extraction Method.
Some practitioners believe that it is only the T/E ratio which is significant, and therefore, as long as E “appropriately” rises with elevations in T, all is well. However, the absolute concentration of E is of concern, too, especially in light of new information pointing to elevated estrogen as cause, or adjunctively encouraging, several serious disease processes, including prostate and colon cancer.
As everyone knows, it is LH which stimulates the Leydig cells of the testes to produce testosterone. A caveat, however: LH has a half-life of only about 30 minutes. When you combine this fact with the absolute pulsatile nature of its pituitary release, care must be taken to not place too much weight upon a single draw. A luxury would be to acquire serial draws, say, twenty minutes apart. However, such would be both inconvenient and probably prohibitively expensive for the patient. The most important reason to assay the gonadotrophins is to differentiate between primary and secondary (hypogonadotrophic) hypogonadism.
The eight hour half-life of this hormone makes it a better marker for gonadotrophin production. It is also less an acute phase reactant to varying serum androgen and estrogen levels than LH. Greatly elevated FSH levels could signal a gonadotrophin-secreting pituitary tumor.
Of note, I run FSH (but not LH) on the follow-up labs, the new third generation (“sensitive”) assay, to determine the magnitude of HPTA suppression secondary to androgen therapy. It also provides valuable information for those patients undergoing TRT who are interested in the state of their fertility.
A very important hormone, and must not be overlooked on initial work-up. Approaching five percent of hypogonadotrophic hypogonadism is associated with hyperprolactinemia, due to inhibition of hypothalamic release of LHRH. Its serum concentration must be maintained within physiological range (meaning neither too high nor too low). Greatly elevated hyperprolactinemia, or hyperprolactinemia plus a Total Testosterone less than 150ng/dL, equals a trip to an Endocrinologist for an MRI of the sella turcica.
True Anti-Aging medicine must be well-familiarized with the ins and outs of this hormone, the only one our bodies cannot live without. Elevated levels can cause secondary (hypogonadotrophic) hypogonadism. I try controlling elevated cortisol with Phosphatidylserine, 300mg QD, with good results. It is just as important to watch for depressed cortisol levels, as well. The assay of choice for that condition is a 24-hour urine.
I have, for my own convenience, omitted the specifics of the obligatory thyroid function panel you certainly will want to run. Hypothyroidism mimics hypogonadism in several of its effects.
This is just good medicine. Ruling out anemia is important, of course, as it may be a cause for the fatigue which brought the patient into your office. You also want to establish baseline H&H, for those rare cases where polycythemia becomes a problem (and we are reminded smokers are at increased risk for polycythemia). Above 18.0/55.0 TRT is withheld, and therapeutic phlebotomy recommended.
Again, just good medicine. Baseline for sodium (which may elevate initially secondary to androgen supplementation) is important. We also want to see LFT’s, as elevations in same secondary to androgen supplementation are listed as a possible side effect in the product literature (although I have yet to see this actually happen). I like the BUN/creatinine ratio as a marker for hormonal hemo-concentration, and also it gives me a hint of how compliant the patient will be (because I always tell them to make sure to drink plenty of water while fasting for the test).
This is drawn to provide your bragging rights when you drop the CHOL 30 points, thanks to your own good administration of TRT. You should expect to see lowered TRIG and LDL’s, too. Be advised, this will not happen if you choose to elevate their androgens above the top of “normal” range, i.e. providing what amounts to an anabolic steroid cycle. Of course, this would no longer constitute TRT, as the practitioner would then be choosing to damage the health and well-being of the patient.
HDL does frequently drop a bit, but that is believed to be due to increased REVERSE cholesterol transport; so much of the plaque is, after being scavenged from the lining of the CV system by HDL, now being chewed up by the liver. Androgens also elevate hepatic lipase, and this may have an effect. The important thing to keep in mind is that TRT inhibits foam cell formation.
For all patients over 40. Even though prostate CA is rare in men under the age of fifty, we don’t want it happening on our watch, do we? At this time, rises in PSA above 0.75 are a contraindication to TRT (until follow-up by a Urologist). You may find that, at the initiation of TRT in older men, when serum androgen levels are accelerating, PSA may, too. This is especially true when transdermal delivery systems are employed, because they more greatly elevate DHT. Once T levels have stabilized, PSA drops back down to roughly baseline. You won’t really see gross elevations in PSA secondary to TRT administration in younger patients. New TRT patients need to be cautioned, and reminded, to abstain from sexual relations prior to the draw, as they may now be enjoying greatly elevated amounts of same.
I get a PSA up front on my over 40 patients, at the one month follow-up in my more senior patients, and every six months after that. DRE (Digital Rectal Exam) is recommended twice per year as well, although the American Academy of Clinical Endocrinologists backs “every six to twelve months” in their 2002 Guidelines for treating hypogonadotrophic patients with TRT.
For those who are considering the addition of GH to their Anti-Aging regimen. IGF-1 will rise from testosterone supplementation, and vice versa. Let’s grab a baseline now, before that happens.
THINGS TO LOOK OUT FOR
CO-MORBIDITIES. Currently, only breast and active prostate cancer are absolute contraindications for TRT. Patients with serious cardiac, hepatic or renal disease must be monitored carefully due to possible edema secondary to sodium retention. Also, TRT may potentiate sleep apnea in some chronic pulmonary disease patients, although studies have also shown it can actually ameliorate the symptoms of sleep apnea.
DRUG INTERACTIONS. TRT decreases insulin or oral diabetic medication requirements in diabetic patients. It also increases clearance of propranolol, and decreases clearance of oxyphenbutazone in those receiving such medications. TRT may increase coagulation times as well.
TESTOSTERONE DELIVERY SYSTEMS
Now we have to decide, TOGETHER with our patient, what form of testosterone delivery system we will START with. There are two basic subsets of same—transdermals and injectables. Here are the current options:
TESTOSTERONE GELS AND CREAMS
The only way to go, in my professional opinion, if physician and patient prefer a transdermal delivery system. They are easy to apply, well absorbed, and rapidly establish stable serum androgen levels (usually by the end of the second day). I recommend all practitioners first try a testosterone gel for their TRT patients.
Much is made of the risk posed by accidental transferal of testosterone to others, such as children or sexual partners. Simply covering with a T-shirt has been shown to block transfer of the hormone. The testosterone sinks into the skin within an hour, which acts as the actual reservoir for the hormone’s delivery. One may then shower, or even swim, without worry. I remind my patients that most of us have neither the time, nor the opportunity, for romance until evening (given the recommended early morning application), and a quick shower is always nice to “freshen up” then anyway.
Gels and creams, like all transdermal delivery systems, provide a bigger boost in DHT levels, compared to injectable testosterone preparations. This can be a double-edged sword. As DHT is responsible for all the things of manhood, the transdermals are better at treating ED than the injectables. However, issues of hair loss and possible prostate morbidity (a contentiously debatable point, to be sure) then come into play. Either way, please make sure to monitor DHT with the transdermals. I’m just not comfortable with gross elevations in DHT, and prefer to avoid adding finasteride whenever possible.
Some have reported an increase in hair growth over the application area(s). All physicians who administer TRT must be prepared to disappoint their patients at this time by pointing out, sadly, this same effect cannot be achieved on the scalp.
These can be quite effective, but are inconvenient to use. Approaching 2/3’s of your patients will develop a contact dermatitis from them at some point. Another drawback is that some patients report they are constantly aware of their placement, and the patches are embarrassingly obvious to other gentlemen in certain public places, such as in the locker room.
The scrotal application variety is the most inconvenient. To see what I would be putting my patients through, I tried them. After just a couple days, I’d had more than enough. Men do not generally enjoy shaving their scrotum, and the patches just do not stay on well anyway. Applying a hair dryer to the patch, as they must be warmed first, is also an annoyance. If you go to the gym during the day, they look strange affixed to the genitals, and must be removed, then reapplied, to shower. They do not stick well in the first place, and even less so once they have been reapplied. Of the two options, I found only the type with the extra adhesive had any chance of remaining in place. The scrotal variety causes the largest increases in DHT—which can be good or bad, as previously explained.
In my opinion, their use is absolutely Stone Age. Sure, they can provide extra revenue by virtue of a billable office based procedure. However, needlessly exposing patients to the risks ALL surgeries pose—hemorrhage and infection—is unwarranted. And the area of insertion will be much tenderer than that following a mere IM injection. But the real issue which selects against pellet implantation is concerned with dosing. Let’s say you establish a “usual” initial dose for the pellets. As will be described in the next section, there is absolutely no way to predict, up front, how a patient will react to a given dose of testosterone, regardless of the delivery system. So you bury these pellets in your patient’s backside, and (hopefully) draw follow-up labs in a month or so. What are you to do if the total testosterone ends up greatly exceeding the top of normal range (meaning the patient hyper-responded to the treatment)? Now you must make a much wider incision to remove them, or a portion of them (and who knows how many to take out?). With their very long half-life, SOMETHING must be done, lest you risk actually damaging the health of the patient by elevating testosterone levels into what might be considered a bodybuilding steroid cycle. And what if the pellets do not elevate T enough? You must bring them back in to implant more, and it’s difficult to sell them on this idea, since they probably are not yet feeling the advantages of TRT enough yet to motivate them into undergoing another surgical procedure. It just doesn’t make sense, to my way of thinking.
Testosterone pellets do have some benefit in that selected patients may believe it more convenient to come in every month or six weeks, and then be done with it for a while. Also, because they release T in a slow, steady rate, the pellets are less likely to induce increases in aromatase activity.
Please watch for coming articles and books by John Crisler, DO on this, and other, continuing subjects related to anti-aging.
03-05-2007, 10:39 PM
More Dr J!
I’ll start out by describing the drawbacks of IM testosterone. They are inconvenient for patients who do not wish to give themselves their own injections, as they must then make weekly trips to your office for same. Why IM test MUST be dosed weekly will be described in detail in another section. Some patients, as you well know, just hate shots (although I have noticed several who had initially claimed this, but admitted, once they had come to enjoy the benefits of TRT, actually came to look forward to their weekly injection). And no doubt, an invasive delivery system brings more risk than, for instance, a testosterone gel or cream (the other best choice for TRT).
When considering dosing of testosterone cypionate, it is important to remember that, due to the weight of the cypionate ester, a 100mg injection delivers, at best, 70mg of testosterone. This is important to keep in mind when comparing the effects of a 100mg weekly injection of test cyp to the 35mg total dose provided by Androgel 5gms QD over the same period.
Many practitioners consider this incredible hormone treatment of choice for hypogonadotrophic (secondary) hypogonadism. Such certainly makes sense, as supplementing with a LH analog indeed increases testosterone production in patients who do not concurrently suffer primary hypogonadism. But often, upwards of 1000IU per day must be given to achieve the desired serum T level. Even then, for some unexplained reason, while serum T levels may be adequately elevated, the patients simply do not report realization of the benefits of TRT, when HCG is administered as sole TRT. You also run the risk of inducing LH insensitivity at that dosage, and therefore may actually cause primary hypogonadism while attempting to treat secondary hypogonadism. HCG, especially at higher doses, also dramatically increases aromatase activity, thus inappropriately elevating estrogens. Personally, I recommend never giving more than 500IU of HCG at a time.
A real benefit of HCG is that it will prevent testicular atrophy. I do not think we should ignore the aesthetics of that consideration. Your patients will feel the same way.
I occasionally hear of physicians trying to use a SERM (Selective Estrogen Receptor Modulator) such as Clomid or Nolvadex, or even an Aromatase Inhibitor (AI), such as Arimidex, as sole “TRT”. All have been shown to elevate LH, and therefore Total Testosterone levels. However, patients report no long-term subjective benefits from these strategies, and the studies thus far reported no long-term changes in lean body mass, fatigue levels, libido, etc. An added risk of using an AI is of driving estrogen levels too low, with deleterious consequences for the lipid profile, calcium deposition, libido, etc.
Finally, Deca-Durabolin (Nandrolone) has no place in TRT. It has a nasty side effect profile, including uncontrollable progesterone-like effects (including gynocomastia) and risk of long-term impotence.
THE MEAT AND POTATOES OF TRT
Now we will delve into the general strategy for administering TRT.
The decision is made, TOGETHER with the patient, which of the various testosterone delivery systems is to be tried first. Be prepared to make adjustments, and try other application methods. You just don’t know which will be best for each particular patient until you try. Besides the simple fact the patient may have a personal preference, or a logistical consideration (i.e. inability/unwillingness to self-inject) for a given application, every-body reacts differently to hormonal manipulation. Some hyper-respond to a given initial dose, others show hardly any bump in serum T levels on same. Yet when you switch to a different delivery system, on initial dosing, they may convert to supraphysiological androgen levels. The same is true of the subjective benefits from TRT. I have patients who love testosterone gel because it successfully treated their ED (the expected outcome because of dramatically increased DHT production), others get more from IM testosterone cypionate. My experience thus far has taught me two lessons: (1) You don’t know how a patient will react to a given dose/system until you try and (2) NOTHING surprises me anymore.
There simply is no way to predict how a particular patient will respond—not Medical History (i.e. number or severity of symptoms), body weight, baseline hormone levels, even anabolic steroid history. I have had very slight gentlemen barely elevate on 100mg of test cyp per week, and massively muscled former steroid athletes who went to nearly two times the top of “normal” range on the same dosage (they had similar baselines). Likewise, one man may see only a modest increase in DHT on 5gms of Androgel, another may become quite supraphysiological on same.
I start my guys out on either testosterone cream/gel 5mgs QD or testosterone cypionate 100mg per week. The IM test cyp must be administered in weekly injections, as opposed to taking twice the dosage every other week. Some physicians even dose every third or fourth week, producing wide swings in serum androgen levels. This puts the patient on an emotional roller coaster, increases the risk of developing polycythemia, greatly accentuates aromatase activity, and actually leaves them lower than they were when they started for the last half of the cycle. In order to get the serum androgen concentration to a stable level more quickly, I “frontload” 200mg the first injection (unless converting over from a gel/cream).
No other medications which manipulate hormone levels are provided until follow-up labs are returned. For IM test cyp patients, the second panel is run following the fifth injection. I also keep in mind the coordination of the injection with the lab draw, as peak serum levels are attained at about the 48 hour point, then fall to about 35% at the one week point. However, by the end of the fifth week, the pharmacodynamics of testosterone cypionate (half life is 5-8 days) are such that relatively stable serum levels are now being produced via weekly injections.
Transdermals can be rechecked in two weeks. They produce stable serum levels, as previously mentioned, for most by the end of the second or third day. Logistically, it makes sense to send the patient for follow-up labs after a fortnight, as there is then time to get the labs back, and bring the patient in, before the initial 30-day supply of the medication runs out. This is better if an adjustment in dosage is mandated by the follow-up labs, or to convert to IM dosing should the patient produce too much DHT. It would be a shame to have the patient refill a script for 5gms of Androgel, when they, by their labs, are going to have their dosage reduced to 2.5gms per day because they hyper-responded to the initial dose, or waste money when what they reallyneed is to be converted to test cyp.
The question of which testosterone delivery system is to be tried first (IM or transdermal) is one which brings much confusion amongst beginning practitioners of TRT. I would, when possible, always start out a patient on a testosterone cream or gel. Ease of application, avoidance of intrusion by injection, and increased probability of successful ED treatment make this so. Also, stable serum levels are attained quickly, determination of successful treatment is more forthcoming (although the manufacturer of this product recommends at least a couple months as adequate trial of therapy). If the labs AND patient’s answers to follow-up subjective report lead to a change to IM testosterone, the conversion is an easy one to make. Simply apply the gel, give the shot, then D/C the gel. However, if a patient is started out on IM test cyp, for instance, yet the patient still does not feel “right” (and thus you may want to try a transdermal delivery system to better raise DHT levels), how are you, given the pharmacodynamics of the testosterone ester, going to safely and successfully dose the conversion to a transdermal?
Dosing changes are made, TOGETHER with the patient, once follow-up labwork is back AND the patient is interviewed regarding their subjective reports of changes in libido, sexual performance, fatigue, strength, mental outlook, etc. Often they will tell you they felt “incredible” the first couple of weeks (and bursting with libido), but they don’t feel quite as good now, but still much better than before they started the TRT. This is because subjective findings are the best while serum androgen levels are accelerating. Adjunctive to this phenomenon is the fact their HPTA was not yet being suppressed, so their endogenous production was higher then than it would be by the end of the month. TRT patients are always HPTA suppressed to greater or lesser degree.
Much weight is placed upon the patient’s subjective findings, as they are not likely to remain compliant in the TRT program unless they feel noticeably better, irrespective of the less obvious long term improvements in CV health, bone density, decreased risk of dementia and cancer, etc. Certainly, if the patient reports they are quite happy at a Total Testosterone level of 600ng/dL, I feel there is little reason to increase their dosage. As an Osteopath, I am loath to provide ANY medication, or increase in dosage, without proven need. As a practical limit, the top of “normal” range for Total Testosterone provides a ceiling, more or less, above which we can expect to find the benefits of TRT beginning to reverse themselves. Actions following androgen receptor binding dramatically improve health and happiness as we go from the hypogonadal state to the top of “normal” range, but beyond that the Lipid Profile and level of insulin sensitivity, for instance, are damaged.
Changes in IM dosing are made in small increments, as response to same is not linear. It is convenient and practical to increase, or decrease IM dosing by 20mg at a time, as this is one “tick mark” on the side of the syringe (for the 200mg/mL concentration). For Androgel patients, we are more limited by their provided dosing whereas we can only either drop down to 2.5gms, or add an extra pack each day (at which time BID dosing may be considered) to reach the 7.5gm, or even 10gm, per day dose. More flexibility is provided through compounded products for those committed to employment of transdermal testosterone delivery systems.
Another risk of jumping the dosage too much is that, should serum androgen levels greatly exceed the top of “normal” range, the patient risks becoming “spoiled” at that level. They would then feel the subjective benefits steroid athletes report, and it would be difficult to get the patient then to be happy at a more moderate—and proper—dose. It is likely you would also therefore produce elevated estrogen activity as well, and further muddy the waters with respect to how the patient feels—and looks (due to emotional changes and even water retention issues from the elevated estrogen). It is far better to make changes in dosing conservatively.
Once the method and dosing is set, by laboratory assay AND subjective report from the patient, then you may address any side effects due to elevated estrogen levels which have occurred. I do not use an AI initially, even when E2 is elevated, because some patients will actually see a drop in estrogen over baseline on follow-up. We would have otherwise added an unnecessary (and relatively expensive) medication. Should the patient develop any “nipple issues” secondary to accelerating serum androgen levels and/or elevated estrogen, you cannot start them on a SERM right away because doing so will invalidate your estradiol assay at follow-up. Of note, males can experience said “nipple issues” even while estrogen levels are within physiological range, due to changes in hormone levels. A drug of the class SERM is treatment of choice in this case, until symptoms subside.
If a patient has “nipple issues”, even while estrogen is within normal range, I add a SERM, emergently. I prefer Nolvadex over Clomid, and Evista is probably best of all for antagonizing estrogen (although much more expensive). Clomid often induces untoward visual effects (i.e. “tracers”), and can cause emotional lability by virtue of its estrogen agonistic effects at the more peripheral (emotion) brain sites. I do like my patients to keep some Nolvadex on hand, should they experience nipple swelling or sensitivity, so they may begin 40mg per day until the symptoms abate, and then taper to 20 mg QD for a few days, then 10mg for a few more, then finally 5mg QD to taper off.
My TRT male patients who suffer E2 elevations above the top of normal range are placed on 0.25mg of Arimidex every third day. If that is not enough, I use the same dose EOD. It is possible to cut the tiny 1mg tabs into quarters, but here a gel or cream preparation, compounded to convenient dosing, makes a lot of sense. A month later I recheck E2, and make further adjustment if necessary. It is important to not lower estrogen too far, which is easy to do with an AI, as doing so has disastrous effects on the Lipid Profile, bone deposition, etc. I prefer to maintain E in mid-range.
So now let’s say we have the patient in a state where Total Testosterone is in the upper quartile of “normal” range, Bioavailable Testosterone is nicely elevated, with E2 safely in check. At this point I offer the patient my HCG protocol. I add in 250-500IU of HCG, on day five, and day six of the week, for those who use the IM injection. In other words, the two days prior to their shot. For those using a transdermal delivery system, every third day. For the IM patients, this compensates for the drop off in serum androgen levels by the half-life of the test cyp. But the main reason is to stave off atrophy of the testicles, by directly stimulating them with the LH analog.
Patients all report they feel dramatically better once the HCG regimen is initiated (and they were properly tuned up on testosterone before they started it). HCG, as a LH analog, increases the activity of the P450 SCC enzyme, which converts CHOL to pregnenolone. Thus all three hormonal pathways are stimulated in patients who may be either entirely, or very nearly, HPTA suppressed. It is my belief this may be a factor in the heightened sense of well-being my patients report throughout the week—far in excess of what a minimal dose of HCG would produce by virtue of induced testosterone production.
Many TRT practitioners add in HCG for a short course every few months, to re-stimulate the testes. My opinion is that it is far better to keep them up to form and function all along the way. The physicians who intermittently use HCG also use it as a “break” in TRT, much the same way hormonally-supplemented athletes manage the typical anabolic steroid cycle. TRT should not be “cycled”. Once I get my patients properly tuned up, I want them to stay that way. They also erroneously believe this allows the HPTA to recover, when it clearly does not. The HCG-induced testosterone production is every bit as suppressive of the HPTA as the TRT, and the supplemented testosterone is still at suppressive serum levels during that time, anyway.
Once the patient is all set, I like to run follow-up labs every six months. It is important to monitor the general health and well-being of the patient, but also insure compliance with treatment protocols and continued effectiveness of same.
****************************** ****************************** ********************
My hope is that the preceding diatribe will gainfully assist the practitioner in implementing Testosterone Replacement Therapy regimens for their qualifying patients. Be prepared, however, to blush as they shower you with accolades following their vast improvements in health and happiness. You may even receive thank you notes from their wives!
03-05-2007, 11:04 PM
From Blesum, all about Androgel
What is AndroGel?
It is a gel with testosterone in it that is rubbed on the skin. Your body then absorbs the testosterone.
Dr. John here at Anabolic Minds is our medical expert on Androgel. Dr. John has stated that he does "a fair amount of teaching for Solvay Pharmaceuticals, makers of Androgel." He also trains "physicians on TRT medicine, as well their Reps." Most of my information comes from his various posts spread all over these forums.
He has expanded more on the actual application process in this thread: questions about androgel
Originally Posted by Dr. John
Here is a copy of my exact instructions for my patients:
HOW TO APPLY TESTOSTERONE GEL
Squeeze all of the gel from the foil packet, the tube, or the number of pumps if using the pump bottle, into a cupped palm. Gently press your two palms together. When you separate your hands, you will have very nearly half of the gel on each palm. Do not rub your hands together. Try to keep the gel on the palms, instead of getting between the fingers. Then simply cross your arms, wiping the gel over your shoulders and upper arms. Thus apply most of it across your upper arms and shoulders. Absolutely avoid the area where they draw the blood from. Finish off by wiping what is left down your FLANKS (sides of your abdomen—not the middle). Then thoroughly wash your hands. Once you have washed them, there is no worry whatsoever about accidental transferal to others, as there is none left on the surface to transfer. Studies have shown this, and also that merely putting on a T-shirt to cover the exposed areas will do the same for the rest of you. If you had to, you could shower in an hour or so, without appreciable loss of testosterone delivery, as the gel soaks into the skin, and the skin acts as the actual reservoir for dispensation of the drug. You wouldn’t want to do this all the time, but swimming or showering in a pinch can be done. It's still a good idea to take a quick shower before engaging in intimacy.
As an alternative with the pump bottle, you can apply half the total number of pumps to one palm, apply to the opposite side of the body, and then repeat for the other side. This makes it less likely to induce waste of the product.
For maximum effect, apply the gel within 3 minutes of showering.
You want a delay of at least two hours after application before drawing labs.
One thing to look for is "frosting" - a white residue on your skin after the alcohol evaporates. This means one of two things, or a combination of both: The Androgel is not being spread around enough, or your skin is not absorbing the product well.
I have only begun using Androgel nearly a month ago. I notice I have a bunch left over on my hand after applying it to my upper and lower arms. What I used to do was to wet my hands with some water and wipe off the excess on my upper thights, thinking I'd get more testosterone for my 5 grams that way until I saw this post from Dr. John in the same thread as above:
Originally Posted by Dr. John
It has been shown that the greater the surface area of transformation, the greater is the proportionate conversion to DHT and E. So try to keep it down. Unless you are having a "testosterone frost", as I like to call it, cut down on the area. So this idea of mixing with water on your hands is not a good idea. Instead, keep the gel in the cupped palm area, so as to not get it amongst the fingers. I know, I know, it takes some work.
He also mentions in the same thread and in another one that it is very important to not apply any androgel on the same day in the area that any bloodwork might be drawn from as it will throw off the numbers considerably.
How can one improve the absorbing qualities of this product?
In this thread, How much DSMO? two options are discussed. The first being using DSMO (an product that improves the transdermal [skin] delivery of products), and the second being rubbing it on one's nuts.
There was a debate on whether DSMO was even a good idea with a prescribed product. The general census was that it could work, but would not be ideal. Going to an injectable if one needed/wanted that much testosterone would be better.
It was also concluded that rubbing it on the nuts was a bad idea due to the high amount of 5 Alpha Reductase in the scrotum and thus a potentially very high conversion to DHT. The nuts' close proximity to the prostate is also rather alarming.
How much of a rise in my testosterone can I expect?
I get my first post-Androgel bloodwork drawn this Wednesday. I will let you know the results. I did see a result posted somewhere here of going from the high 100's to the low 800's on 5g a day.
What kind of products should be run alongside with Androgel? I have not done much research into this yet. This is just what I have in my notes currently - I will be doing more research soon.
HCG: Prevents testicular atrophy. Somewhere I saw a recommendation of 100 IU 3 times a week. Bobo warns that constant use of HCG is bad news with the body desensitizing down the road.
Amiridex: Lowers/controls estrogen. Saw a recommendation of 0.25 (failed to write if g, mg, iu or what) 3 times a week.
Administrator B5150 here is on Androgel HRT as well and often has some good answers on Androgel related questions. He encourages exfoliating the application area with a loofah of some sort in the shower prior to application.
This post will be updated as I discover more information or get corrected if there are any mistakes I might have made. I just wanted to put together a post that I wish existed when I began my research so others wouldn't have to spend so much time working the search function.
If you have any questions, ask away and they'll be added to this post along with the answers.
Last edited by plymouth city; 03-05-2007 at 11:05 PM. Reason: none
03-07-2007, 12:33 AM
good reading, my eyes hurt now and so does my brain....what was the point of reiterating all of that?
03-07-2007, 10:40 PM
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