THYROID:

Generally, it is useful to improve thyroid hormone signaling before adding testosterone. It sets the foundation for testosterone replacement in order to minimize adverse effects.

The brain is a separate compartment from the body when it comes to thyroid hormone. The brain can have different levels from the body. Outside of doing a lumbar puncture to help determine brain levels, the TSH actually is a measure of what is in the brain. Free T3, Free T4, Total T3, Total T4, and Reverse T3 indicate what is in the body.

When body levels are high, yet TSH is also high, there may be a problem with either thyroid transport into the brain or thyroid activation by Astrocytes in the brain. The problem then becomes how to improve brain levels so that mental function can improve. When body levels are already high, increasing thyroid hormone further may result in hyperthyroid symptoms in the body such as heart palpitations or arrhythmias. Assessing for and addressing metabolic-nutritional problems which can cause transport or activation problems in the brain for thyroid hormone would be a focus of treatment. If thyroid resistance as a possibility, particularly if a person shows signs of hypothyroidism despite high body levels, then it may be possible to add thyroid hormone to improve function.

TESTOSTERONE:

Using anti-estrogens isn’t often needed when doing testosterone replacement treatment.

When testosterone level is optimized to between 650-900 ng/dL, the testosterone signal will often counteract problems with estrogen if they happen at all. As per Endocrine Society guidelines for testosterone replacement, I would go ahead and treat the hypogonadism. If frank problems with estrogen occur – such as gynecomastia, would it be necessary to add an anti-estrogen. Worrying about this issue excessively would simply mean postponing the benefits of restoring testosterone signaling. Techniques to minimize estrogen signaling with testosterone replacement include using transdermal testosterone – and applying it only to the arms and shoulders, and using smaller and more frequent testosterone injections – such as twice or more a week injections.

If adrenal cortex hormones are low and thyroid hormone is suboptimal, then problems may occur with the addition of testosterone. Testosterone suppresses adrenal cortex signaling and exogenous testosterone can reduce thyroid hormone production. Both actions may exacerbate ongoing problems.

DEPRESSION:

Antidepressants generally work on only a small portion of what causes depression. This is why they usually do not work when used alone.

In my experience, it takes multiple problems in one’s body to cause a mental illness – so many problems that the body/mind is unable to mount a compensatory action to maintain function. In depression, these problems summate so that a primarly pro-inflammatory state occurs. These problems may occur in multiple areas such as the nervous system, immune system, endocrine system, gastrointestinal system, metabolism, and nutrition. It is important to do as complete an assessment as one can in at least these areas to identify the underlying causes of depression. The assessment includes taking a history, doing a physical exam, doing lab tests, etc. Once identified, a treatment may then be developed to address each one.

ANXIETY:

Anxiety generally means the sympathetic nervous system is over-activated. This activates problem solving and threat assessment circuits in the nervous system as well as the immune system and other systems of the body.

The question to answer is why is the sympathetic nervous system activated in the first place. Is there an external threat? Is there a psychological threat. Are there internal problems such as infections, metabolic-nutritional problems, which activate the sympathetic nervous system. The assessment – like in depression – goes over multiple areas of the body/mind to help identify causative factors. In general, there usually are several underlying causes which together overwhelm the body/mind’s ability to compensate and maintain function.

Anxiolytic medications such as benzodiazepines help reduce anxiety but generally do not address the underlying cause. Some of the causes may worsen over time – e.g. hormone status, nutritional status, infection, etc. This can then overwhelm what an anxiolytic medication can do. If the underlying causes are not directly addressed, then multiple medications may be necessary to control symptoms of illness and help improve function.

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DEPRESSION:

When treating depression, it is useful to find an antidepressant which isn’t causing intolerable side effects. Even if it isn’t causing improvement, I would consider it one component of treatment – the one that addresses a nervous system component of depression.

Once this is established, other medications including thyroid hormone can then be added to “augment” treatment. This is fairly standard technique found in textbooks. Some of these augmenting agents include:
1. Liothyronine (T3, Cytomel) 25-50 mcg a day – this is done even without lab testing
2. Lithium Carbonate 300-900 mg a day
3. Atypical antipsychotics such as Seroquel 50-150 mg, Abilify 5 mg a day
4. Adding another antidepressant that works in a different way – for example combining Citalopram with Wellbutrin

It is useful for patients to learn more about their illnesses to arm themselves with information when discussing options with their doctors. This may be much more important in other countries where physicians tend to be conservative or rigid. One thing one can do is to simply get a textbook of psychiatry to learn about the mental illnesses and treatments.

For example, in Germany, one can find such textbooks on Amazon.de http://www.amazon.de/s/ref=nb_sb_noss/278-5316272-0503167?__mk_de_DE=%C5M%C5Z%D5%D1&url=search-alias%3Daps&field-keywords=Lehrbuch+der+Psychiatrie

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HIGH DENSITY NUTRITION:

Since nutritional deficiencies make up a large component of the underlying causes of mental illnesses such as depression, I generally try to help patients improve in function by achieving high nutritional density in their diets.

A good starting point for learning about high density nutrition is the book “Nourishing Traditions” by Sally Fallon and Mary Enig http://www.amazon.de/Nourishing-Traditions-Challenges-Politically-Dictocrats/dp/0967089735/ref=sr_1_1?ie=UTF8&qid=1353739866&sr=8-1

When patients cannot change their diet adequately to obtain high nutritional density, I will then prescribe nutritional supplements to improve nutritional status.

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TESTOSTERONE REPLACEMENT THERAPY:

Basic testosterone replacement therapy is simple: add enough exogenous testosterone (via transdermal gels or injections or other means) until the total testosterone is midway in the reference range. This is the general recommendation of the world organization for endocrinology, Endocrine Society, in their treatment guideline.

Until one gets an adequate amount to reach the target, the treatment is not sufficient and inadequate.

If options are limited in one’s country, use whatever option there is to the fullest to achieve the target goal.

Transdermal testosterone will always raise DHT since skin can have a lot of 5-alpha reductase to convert testosterone to DHT. The higher DHT is generally not a health risk. It is a risk for accelerating male pattern hair loss in men who have high scalp 5-alpha reductase production. This is generally genetically determined.

Yes, there are complexities in testosterone replacement therapy. DHT and estrogen levels are considerations. Thierre Hertoghe in Belgium and his partners are one of the most skilled practitioners in this regard in Europe.

But before anything else, an adequate dose still has to be achieved before discussion of the effectiveness of treatment can be done.

Here is a good review article:

T3 augmentation in major depressive disorder: safety considerations.
Rosenthal LJ, Goldner WS, O’Reardon JP. Am J Psychiatry. 2011 Oct;168(10):1035-40.
PMID: 21969047

http://www.ncbi.nlm.nih.gov/pubmed/21969047
http://ajp.psychiatryonline.org/article.aspx?articleid=178261

Excerpts from the article:

Augmentation of antidepressants with T3 is one of the oldest evidence-based treatments for major depressive disorder.

In 1969, Prange et al. conducted a pivotal study (8) demonstrating that administration of liothyronine en- hanced response to tricyclic antidepressants in patients was monitored, but methods available at that time were not sensitive or specific. … Many subsequent studies have confirmed the Prange et al. study’s finding of efficacy, but few have formally assessed the HPT axis during treatment.

Joffe and Singer (4) evaluated T3 versus T4 in a randomized trial and found significant changes after 3 weeks in T3, T4, free T4, TSH, and T3 resin uptake in both groups, but these changes were not positive predictors of response; the main finding was that T3 was more effective than T4 as an augmenter.

Two studies of T3 in combination with SSRIs included baseline and follow-up thyroid testing. In the first, Cooper- Kazaz et al. (21) compared sertraline (50–100 mg) combined with either T3 (25–35 μg) or placebo in an 8-week study and found that the sertraline-T3 combination produced superior response and remission rates. After 8 weeks of T3 supplementation, the mean TSH level fell significantly from 1.70 μIU/ml at baseline to 0.28 μIU/ml in responders, whereas nonresponders had mean pre- and posttreatment levels of 1.88 μIU/ml and 0.76 μIU/ml, respectively; responsiveness to treatment was significantly correlated (p=0.01) with the change in TSH level, suggesting that the therapeutic benefit could have been due to changes in the thyroid axis in this population. In a post hoc analysis, baseline T3 levels in patients who responded to T3 augmentation were significantly lower than in those who did not respond (107.60 ng/dl compared with 137.4 ng/dl, p=0.002).

Recommended Safety Guidelines for T3 Augmentation of Antidepressant Medication include:
1. Obtain baseline TSH, free T4, and free T3 levels prior to augmentation.

2. Recheck thyroid indices at 3 months and then every 6 months, or at minimum annually. The goal is for the TSH level to be at least at the lower limit of the normal range (around 0.4 μIU/ml) or below in the absence of hyperthyroid symptoms. Free T3 level can be maintained at the upper limit of the normal range based on the severity of depressive symptoms and response to T3.

3. In the longer term, if the patient has a history of multiple episodes or significant treatment resistance, maintenance on T3 is reasonable as an open-ended treatment option. If there are no symptoms of hyperthyroidism and no known cardiac disease, consider maintenance T3 supplementation even if the TSH level is below the normal reference range, depending on clinical efficacy.

Note that the dose used in studies is 25 mcg of T3. T3 is superior to T4 for treatment of depression.

The goal is a TSH at or below 0.4 uIU/mL – without showing signs of hyperthyroidism.

In patients with depression, it is very common to see suboptimal thyroid signaling – either the TSH is excessively high or body levels are suboptimal. Depression often has strong proinflammatory and nutritional deficiency components. These will impair thyroid signaling. The addition of T3 to restore thyroid signaling is thus a logical intervention.

@grif 6763 wrote:

A few more short questions:

2) You said: “When body levels are high, yet TSH is also high, there may be a problem with either thyroid transport into the brain or thyroid activation by Astrocytes in the brain. The problem then becomes how to improve brain levels so that mental function can improve.” Is this something which an ordinary endocrinologist or psychiatrist should know how to deal with? Does it make sense to bring this up or will this fall through their filter?

3) I noticed that the hair on my hairline looks different. It’s shorter than the other hair and the hair also looks thinner. Do you know if Propecia or Rogaine would be an option? I read bad stuff about both of them. Or are there other safe options?

Question 2: This isn’t something an endocrinologist would think about. However, if they use TSH as the primary measure of thyroid function, then adding thyroid hormone to lower TSH is the next logical step if the person has signs of hypothyroidism. In regard to the psychiatrist, the answer is again “no”. But thyroid augmentation with a target TSH of below 0.4 is an established standard treatment for depression, particularly to improve the response to antidepressant treatment.

Question 3: Since depression has a large component consisting of excessive pro-inflammatory cytokine signaling, adding Propecia without first addressing the causes of depression is risky since it prevents the brain from responding adequately to counteract inflammatory signaling. This could lead to negative metabolic changes, impaired functioning, and the possibility of structural damage (e.g. brain cell death).

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COMPLEX ILLNESSES:

When faced with a complex illness such as depression – which generally has multiple simultaneous underlying causes, it is important to first discover what those underlying causes are then address each one in treatment. This would then maximize the chances of a positive outcome while minimizing the negative effects of treatment.

One way of organizing the causes is to organize them at four levels of organization:

1. STRUCTURAL PATHOPHYSIOLOGY: this includes infections, allergies, obesity, brain injury, gastrointestinal illness, cardiovascular illness, respiratory system illness, autoimmune illnesses, genetic predisposition for illness, etc.
2. SIGNALING PATHOPHYSIOLOGY: this includes excessive or suboptimal levels of various signals – hormones, cytokines, neurotransmitters, etc. Lab testing can be done for most of them.
3. METABOLIC AND NUTRITIONAL PATHOPHYSIOLOGY: this includes the ability to maintain adequate body temperature (thermogenesis), dyslipidemia, blood sugar production, nutritional excesses or deficiencies. Many can be lab tested.
4. PSYCHOSOCIAL AND ENVIRONMENTAL PATHOLOGY.

Each system in the body is evaluated in the history, physical, and through lab tests to help determine each of the underlying causes of a mental illness. The causes are organized as above. Then each is address the best that we can with treatment.

Another way to help improve understanding of ones illness is to list every symptom one is experiencing. Once done, they can then be organized in groups that are related – e.g. symptoms related to depression, symptoms related to other health problem.

Often, many illnesses have common underlying causes. For example, diabetes, heart disease, obesity, hypertension, mental illness, fibromyalgia, migraine, etc. have many commonalities. Thus addressing each of the identified underlying causes may not only improve mental function but physical health problems also.

Am I reading correctly that your Total Testosterone level is far below the bottom of the reference range?

If so, getting to upper quartile may go a long way to helping you feel better.