Great post from Dr Mariano...

[HRTstudent]

Figured you might like to read this. This guy is very open and a true wealth of knowledge for guys like us who constantly collide with doctors who know next to nothing about TRT, yet continue to prescribe it.

http://www.definitivemind.com/forums...read.php?t=875


Every thought, behavior or symptom is a summation of all the activities within cells in the body (metabolism) and the effects of their molecules (signals such as neurotransmitters, hormones, etc. and nutrients).

Cells of the body form groups for specialized functions. Large groups of cells are called systems.

I focus on several large ares to examine for problems which can summate to a person's illness, which can give fairly straightforward targets for treatment that give a lot of bang for the buck. These areas include the nervous system, endocrine system, immune system, the gastrointestinal system, hepatic signaling function, metabolism and nutrition. These areas all interact with one another.

Fatigue or the lack of energy has many factors including:
1. suboptimal signals that promote energy and metabolism such as thyroid hormone and norepinephrine/adrenaline.
2. excessive signals that reduce energy and impair metabolism such as excessive pro-inflammatory signaling.
3. suboptimal nutrition - which includes a large number of vitamins and minerals that need optimization to improve. For example, optimizing iron is one area of importance to menstruating women who lose large amounts of iron with each period.
4. suboptimal production of adrenal hormones, including aldosterine, cortisol, etc.
5. suboptimal estrogen or testosterone - though many times this is a smaller issue that the ones above.

Brain fog is a very general term which usually includes difficulty in thinking, concentrating, memory.
1. Many of the factors contributing to fatigue also contribute to brain fog.
2. The brain's microglia and astrocytes can send pro-inflammatory signals as part of their immune system function.
3. Inflammatory illnesses (e.g. autoimmune illnesses, infections, allergies, etc.) can increase inflammatory signaling which is then transmitted to the brain to change behavior.

Anxiety is an emotion which is triggered by excessive norepinephrine signaling, uncontrolled by other signaling systems. Norepinephrine is the primary signal of the sympathetic nervous system that is involved in fight or flight behavior. Heart rate can be elevated as well as blood pressure by norepinephrine in excess. Note that norepinephrine signaling, itself, increase pro-inflammatory signaling throughout the entire body.

Progesterone is an anti-inflammatory signal in the brain. It's daughter signal allopregnanolone is another important anti-inflammatory signal. Progesterone also works through the GABA signal system to reduce norepinephrine signaling helping reduce anxiety, stress, and seizures.

The problem with progesterone is that it is a precursor (can be converted) to other hormones which can cause a cascade of events leading to the opposite effect.

For example, progesterone can be converted to the estrogens. It increases receptors for the estrogens, making one more sensitive to estrogen. The estrogens can promote aggression, anxiety, and inflammatory signaling if in excess. They can also reduce available thyroid hormone - leading to fatigue, increased anxiety. Both effects can lead to panic attacks.

Testosterone is a very calming signal. However, it can be converted to estradiol and other estrogens, causing problems if the estrogens are in excess, causing problems in other systems.

Free testosterone is such a small part of the total testosterone signal that I do not use it as a measure of testosterone's activity. Free testosterone is further determine by numerous other hormones. Thus, when free testosterone is low, the question is what is happening with those other hormones - e.g. estrogen, insulin (e.g. diabetes), progesterone, thyroid hormone, etc. I prefer monitoring total testosterone because it also gives me an idea of the dose of testosterone needed for replacement therapy.

There are a lot of areas that can have potential problems in the body and there are a lot of interactions.

One way of approaching it sequentially is to:
1. optimize nutrition
2. evaluate for and address immune system problems (including gastrointestinal problems, which are commonly immune system problems).
3. optimize thyroid hormone
4. optimize nervous system function - e.g. controlling norepinephrine, dopamine, serotonin signaling, improving sleep quality, etc.
5. then if needed, optimize adrenal hormone signaling.
6. then if needed, optimize reproductive hormone signaling.
7. then if needed, other optimizations including growth hormone.

Each stage self-corrects problems in later stages. Adrenal problems generally reflect problems within the nervous system, immune system, and other hormone systems. Addressing these reduces the need to directly add adrenal hormones - this is often an imbalanced and unstable treatment with many possible downsides.

Often times, practitioners overly focus on testosterone, progesterone, and estrogens. But for behavioral problems, there are other much more important problems to address first that give one much more bang for the buck when it comes to improvement. For women, addressing these areas often eliminates the need for using estrogen, testosterone, and progesterone except for more limited targets of treatment - e.g. hair growth, acne, heavy periods from excessive estragen, bone metabolism, memory, etc.

Best,
Dr. M

[kelkel]

Outstanding read HRT. I actually put in a post the other day how many docs are now using TT as their measurement as it's basically the pool that is pulled from and the reserve as well.

Good stuff. Thanks!

[Renholder]

Dr Mariano is very knowledgeable, but at the same time, he further cements how difficult getting to the bottom of these type problems are, considering that most of us don`t have acccess to doctors of his calibre.

There is simply so much that could be causing similar symptoms.

[Times Roman]

I read this on his website the other day. I need to read it a few more times to really have it sink in. Thanks HRT for pointing me in the direction, really a lot of good stuff there....

[Vettester]

Sorry guys, I don't agree with his assessment of free testosterone , and that it's a "small part" of the total testosterone signal thing. He even says that when it's low, you need to question what's going on with other hormones. Thus, IMO, that's just one more reason to include it on the list of assays, as it will help counterbalance the determination for what's needed with your personal program.

[jimmyinkedup]

I didnt know there was that relationship between progesterone and estrogen / estrogen receptors. I actually though it was converse to what he stated to be honest. Im researching now.
I love this forum.

[steroid.com 1]

Mariano has his fans and he has his detractors as well...this is an art and not a science.

His cascade approach is one more advanced practitioners in the TRT space would only know; don't expect GP's, Endo's or Uro's to get this...no way.

Some of his comments are basic and obvious like Testosterone being a calming signal but that it can be converted to estradiol and other estrogens, causing problems if the estrogens are in excess, causing problems in other systems...we know this and we know how to manage it.

It's a good post and Mariano has a unique way for managing sex hormones in men.

But remember, he's just one Doc with his opinion...there are others of course.

BTW, I agree with you Vette on his opinion of Free T versus Total T...there are many in the know who would disagree with that for sure.

[bp2000]

Notice he starts with nutrition then the CNS and Adrenals before he looks at Testosterone i.e. sex hormones. He looks upstream before going to the nut's. IMO smart way to do it as if the subsystem's are off it can throw off testosterone.

[HRTstudent]

Notice he starts with nutrition then the CNS and Adrenals before he looks at Testosterone i.e. sex hormones. He looks upstream before going to the nut's. IMO smart way to do it as if the subsystem's are off it can throw off testosterone.

Totally agree...

Nutrition and lifestyle are so important, BUT if we are going for quality of life where else is a better place to start? My current doctor shares a similar view on the importance of nutrition. He basically said that if you aren't eating right then TRT and all this hormonal stuff is a waste of time. To a large degree, its probably true unless you have something akin to 0 pituitary function