Functional Endocrinology

Functional Endocrinology

A New Paradigm in Balancing Hormones

The dominant approach in western medicine when it comes to balancing hormones is based on the assumption that there are no restorative capabilities of the endocrine system; that is, if function is lost replacement therapy is the primary alternative.

However, physicians that provide hormone replacement without consideration to the causative reasons for the imbalance, as well as the alterations that might be created by the replacement, have no respect or understanding for human physiology.

It is imperative to understand the physiological functions and alterations in metabolism that are occurring within hormone imbalances. The first step should be to apply conservative therapies such as diet, nutrition and lifestyle changes to optimize and modulate the physiology rather than simply supplying agents (hormones) that dominate over physiology to manage the symptoms.

This is where functional endocrinology enters the picture. The functional approach is based primarily on the principle of restoring function to:

  • Improve physiology
  • Enhance a person’s ability to make any hormones they may be deficient in
  • Improve the ability to modulate and regulate the endocrine system

The endocrine system is basically a series of glands that release hormones that are intercellular chemical agents. These chemicals are communicating information to our tissues and cells, telling them how to respond.  An evaluation of the endocrine system, tells us how well the body is communicating, how effectively messages are being sent and received and how well these messages are being responded to.

When we look at endocrine function in this way, the endocrine patient is no longer thought of as just a menopause patient, for example. We understand that all disease processes may be initiated or worsened by alterations within the endocrine system and the ramifications go far beyond hot flashes and diminished libido.

To summarize, there are two different approaches to hormone balancing; replacement and functional. If we have a patient with low progesterone, for example, the replacement approach will prescribe progesterone as the means of therapy. The functional approach will address why the progesterone is low. For example, if a menopausal patient has low progesterone, it may be because they have low adrenal function since the majority of progesterone produced during menopause is from the adrenal glands. On the other hand, if we have a menstruating woman with low progesterone levels, we need to consider factors impacting the pituitary-ovarian feedback, like a decrease in Luteinizing Hormone (LH) output due to adrenal cortisol elevations.

The functional approach involves a much more in depth thought process than the replacement approach. This is not to say that hormonal replacement lacks value. There are indeed times that replacement is beneficial or necessary. However, our starting place in functional endocrinology is the evaluation of factors underlying the hormonal imbalance and seeing if we can restore proper function.

Laboratory Testing
There are three different methods used to measure hormonal levels; blood, saliva and urine testing. Each method has certain advantages and disadvantages.

The primary method utilized by allopathic doctors is blood testing. Blood tests offer the great benefit of being able to test virtually every conceivable hormone. Urine and saliva testing cannot measure as large of a variety. The great majority of blood tests ordered are measuring hormones that are bound to proteins. Hormones are protein-bound as they move peripherally through the blood to their cellular target site. However, when a hormone is bound to a protein it is not active. It needs to shed the protein and become free-fraction to be active and available to bind at a receptor site. Thus, protein-bound hormones are not the best method to measure the effects of hormones at cell receptors sites. Free-fraction hormones levels can be measured via blood, but these tests are generally quite expensive. If a lab test stipulates free testosterone, for example, it is measuring the free-fraction hormone. If it doesn’t say ‘free’ it is generally a protein- bound test.

It is not uncommon to see protein-bound levels of a hormone to be normal (or abnormal) while the free-fraction hormone reading gives the opposite information.  Salivary tests measure only free-fraction hormones (in their active state) and are quite reasonably priced in comparison to free-fraction blood tests. For this, and many other reasons, salivary testing is highly preferred for functional evaluations.

Other benefits of salivary testing are that we can evaluate the circadian rhythm of hormones such as cortisol and melatonin as they are released throughout the day. We can also measure female hormone levels through an entire menstrual cycle allowing us to see imbalances in different phases of the cycle. We need to see these fluctuations to understand the bigger clinical picture.

While not fully accepted by the greater medical community, there are several hundred studies demonstrating the sensitivity and specificity of salivary testing.

Urine testing cannot accurately measure whether a person is producing too much or not enough of a certain hormone. Urine measurements are an expression of hormones that have gone through detoxification pathways in the liver and kidneys. Depending on detoxification and clearance rates, urine readings may not be reflective of actual hormone levels in the blood and tissues.

However, urine testing is highly effective in measuring how hormones are metabolizing. Urine tests can be used to measure certain estrogen metabolites that have been linked to estrogen proliferative disorders like breast cancer.

Metabolic Assessment
In addition to salivary testing, we utilize a comprehensive Metabolic Questionnaire to assist us in the evaluation of functional disorders and their relationship to endocrine imbalances. We also perform comprehensive blood chemistry analysis to gain a deeper understanding of the functional status.

There are four key areas that we need to identify and manage to be successful in treating endocrine disorders from a functional perspective:

Identify and manage adrenal and blood sugar disorders. Disorders in blood sugar and adrenal function can cause major defects in the ability to produce hormones like progesterone, testosterone and DHEA. These disorders are an absolute priority and have to be managed if we are to be successful in functionally balancing hormones. Go to our Members Only area and download our articles on Blood Sugar and Adrenal Disorders.

Identify any GI disorders and food sensitivities. These factors can drive the adrenals and cause local and systemic inflammatory responses.  Conversely, many aspects of GI function are impacted by endocrine function and give us clues of underlying functional disorders. For example, proper digestion of proteins is greatly impacted by thyroid function. Estrogen elevations, in both men and women, negatively impact the breakdown of fatty foods leading to certain digestive complaints. Constipation can be the consequence of metabolic changes brought on by an under-functioning thyroid gland.

Identify and manage any alterations in detoxification capabilities of the liver. Impairment in these pathways (often a consequence of too much hormone intake or too many medications) can lead to excess circulating hormones impairing receptor site sensitivity.

Identify and manage any imbalances in essential fatty acid metabolism. Fatty acids are used to metabolize and produce hormones. Imbalances in fatty acids can also impair proper utilization of hormones at their receptor sites.

Pituitary Dysfunction
Pituitary function must be considered in all endocrine disorders. Pituitary dysfunction is reflected in Cortisol, LH, FSH, Estradiol and Testosterone levels.

Pituitary hypo-function is characterized by: diminished sex drive; all manner of menstrual disorders; lack of menstruation.

We often see pituitary hypo-function in female patients following pregnancy. Pituitary suppression can occur due to the high hormones levels produced during pregnancy. We also see this condition in female patients who have been on ‘the Pill’ for a long period of time, as they tend to lose their pituitary-ovarian feedback loop causing the pituitary function to become sluggish.

Pituitary hypo-function can also be a consequence of elevated cortisol levels and insulin resistance causing diminished pituitary function. Adrenal function and blood sugar balance must be brought under control in these situations.

Nutritional support of pituitary hypo-function must always consider the free-fraction hormone levels and can include the herbs Tribulus, Maca, and Panax Ginseng along with the mineral Zinc. These compounds have somewhat different effects in males and females. In males, they tend to increase LH levels which help to produce testosterone, while in females they tend to increase FSH levels which produce estradiol.

In females, when we want to support both the pituitary and increase LH levels and progesterone, we can use the herbs Chasteberry and Shepherd’s Purse.

For females with Post Birth Control Syndrome, all of the above substances can be given for several months until pituitary function is restored.

Prostate Conditions
Prostate hypertrophy is really common in men. Most men will have some degree of prostate hypertrophy as they age. Symptoms include: urination difficulty or dribbling; frequent urination; pain inside legs or heels; feelings of incomplete bowel elimination; nervous legs at night.

There are different shifts in metabolism that can cause these problems. One of the things we can measure, in a salivary test, is increased Dihydrotestosterone (DHT) production. This hormone increases proliferation and growth of the prostate.

Patients with elevated DHT can benefit from: Zinc, Saw Palmetto, Stinging Nettle, Glycine, L-Glutamic acid and L-Alanine.

One of the factors that can cause elevated DHT is decreased production of progesterone. Progesterone in a male is made by the adrenal glands. So, adrenal dysfunction can lead to low progesterone levels (which can lead to increased DHT and prostate hypertrophy). For these reasons, managing adrenal and blood sugar disorders can be crucial in the management of prostate issues.

Another common hormonal shift that can cause prostate hypertrophy is elevated estrogen. Estrogen tends to keep DHT in the prostate tissue instead of being cleared out. This has the effect of stimulating proliferation. Males with this condition can benefit from: Genistein, Indole-3-carbinol, Pyridoxal-5-phosphate (B6), Black Cohosh, Dong Quai and methylation cofactors like B12 and Folic acid.

Also, extremely beneficial for prostate problems is essential fatty acids (especially from flax seed).

Andropause
One of the most overlooked conditions in health care today is andropause, sometimes referred to as male menopause. This condition relates to the physiological state when a man is no longer testosterone dominant. This condition once thought to affect primarily middle-aged and older men is often seen today in teenage and younger men. Andropause is a reflection of the status of four hormones; DHT, Testosterone, Androstenedione and DHEA.

Symptoms include: decreased libido; decrease in spontaneous morning erections; decrease in the fullness of erections; muscle soreness; unexplained weight gain; increased fat distribution around the hips and chest; decrease in physical stamina; episodes of depression.

Different substances can be effectively used to help restore androgen dominance. Testosterone production is stimulated by the pituitary gland via the release of LH. When LH is low, we can use the following substances to increase LH and Testosterone levels: Tribulus, Maca, Panax Ginseng and Zinc.

Andropause can also be related to insulin resistance, with lab tests showing elevated fasting glucose and triglyceride levels. These men have the tendency to over-convert testosterone into estrogens. This pattern can often be difficult to unlock and manage as it is necessary to unlock all sides of the pattern by improving insulin sensitivity through diet, exercise and specific supplementation while also slowing down the over-conversion of testosterone, with specific bioflavonoids, and helping to modulate the estrogen receptors with specific compounds such as Genistein and Indole-3-Carbinol.

Menstruating Females
In menstruating women, we look at the following symptoms of endocrine imbalance: alternating menstrual cycle length; extended menstrual cycle (greater than 32 days); shortened cycle (less than 24 days); pain and cramping during periods; scanty blood flow; heavy blood flow (usually a consequence of progesterone insufficiency); breast pain and swelling during menses; pelvic pain during menses; irritable or depressed during menses; acne break outs; facial hair growth; hair loss and thinning.

As a woman gets older, we also want to assess whether there are signs of perimenopause such as missed menstrual cycles or any recent alterations in the cycle. Perimenopause brings great fluctuations in hormonal output. Testing of reproductive hormone levels during this time is very difficult to evaluate. It is much preferred to measure adrenal cortisol and DHEA levels and balance the underlying functional factors that we discussed earlier.

For menstruating women (prior to perimenopause), we usually run an adrenal panel at the outset. For more difficult or complex cases, we can run a salivary hormone panel that collects 11 samples throughout the cycle. This test measures levels of Progesterone, Estradiol, LH, FSH, Testosterone and DHEA.

With menstruating women, it is much preferred to treat them functionally rather than with hormone replacement. When you give a menstruating woman a hormone, you are dominating over their pituitary-ovarian feedback loop which can make it much harder for them to get their feedback loop cycles back in balance.

To support progesterone production, we can utilize herbs such as Chasteberry and Shepherd’s Purse.

To modulate estrogen levels, we can manage estrogen receptor sites using compounds such as Genistein and Daidzein that function as “Selective Estrogen Receptor Modulators”. The herbs Black Cohosh and Dong Quoi have strong estrogen modulating impacts on the metabolism without the adverse risks of estrogen replacement therapy.

Blood sugar and adrenal management is required in most of these cases.

Menopausal Females
In menopausal females, insufficient production of reproductive hormones can produce symptoms that include: uterine bleeding since menopause (a red flag for possible malignancy); hot flashes; mental fogginess; disinterest in sex; mood swings; depression; painful intercourse; shrinking breasts; increased vaginal pain; facial hair growth; acne; dryness or itching.

Via salivary hormone panel, we measure levels of free-fraction Cortisol, DHEA, Estradiol, Estrone, Estriol, Progesterone and Testosterone, LH and FSH. Depending on the results of these tests, we then re-balance the adrenals and blood sugar, modulate estrogen receptors, support progesterone levels and/or support liver detoxification of elevated hormone levels. We also evaluate the blood for any underlying factors that could be functionally disturbing hormonal balance.

In certain cases, however, when a menopausal woman has lost her hormone reserves, she can benefit from bio-identical hormone replacement. Alongside with replacement, we continue to manage functional factors.

The Impact of Other Hormones on Thyroid Metabolism
In our Members Only page, we have a detailed download on  Thyroid Assessment and Nutritional Management. This is a very detailed account on all aspects of thyroid function and dysfunction. The medical focus on the hormone TSH, in thyroid disorders, often causes physicians to miss other hormonal shifts that can be causing the thyroid symptoms. In this article, we will look at the effects of other hormones on the thyroid. This information can often unlock difficult and poorly responding thyroid cases.

Elevated estrogens increase Thyroid Binding Globulin levels which increase rates of the thyroid hormone T4, but in a protein-bound state, rather than in the active free-fraction state. In this scenario, we don’t get a tissue response to the bound T4. This results in thyroid symptoms. This situation must be considered in people who are on estrogen replacement therapy.

Testosterone elevations, which are very common in women, cause the thyroid to over-convert from T4 into T3. We then begin to see increased levels of T3, which can lead to T3 resistance at the receptor sites. When there is too much of any hormone, the receptors sites tend to shut down. Elevations of testosterone, in women, are generally the result of insulin resistance.

Elevated levels of cortisol can impact thyroid metabolism by decreasing T3 (which is the active thyroid hormone) and by suppressing TSH, which signals thyroid hormones to be produced. Elevated cortisol also has the potential to cause thyroid resistance. In these cases, thyroid blood markers may be normal, but the person has thyroid symptoms since thyroid hormones cannot bind at their receptor sites.

Progesterone has an impact on the thyroid by stimulating thyroid peroxidase enzyme (TPO) which helps increase thyroid hormone production. Decreased levels of progesterone will lead to reduced TPO and thyroid hormone production.

Pregnenolone Steal
All of our steroid hormones come originally from cholesterol. Cholesterol is converted into the hormone pregnenolone. Pregnenolone is considered the ‘mother hormone’ as it will convert into all of the other steroid hormones (such as DHEA, progesterone, testosterone and the estrogens).

Pregnenolone conversion is directly related to adrenal status. The adrenals trap pregnenolone and store it. Under times of stress, when the adrenals are in an alarm state (with high cortisol levels) or a state of fatigue (with low cortisol levels), pregnenolone is converted into cortisol to support the stress needs of the body. This takes place at the expense of pregnenolone conversion downstream into reproductive hormones as the body prioritizes handling stress over reproduction. This phenomenon is called Pregnenolone Steal. Pregnenolone Steal creates a problem because there is only a limited amount of pregnenolone produced each day in the adrenal glands and there are often insufficient levels to meet demand when there is a stressful event.

Let’s clarify what we mean by a stressful event.  We are not only speaking of psychological stress, but also physiological stress factors such as blood sugar spiking up and down, insulin resistance causing strong surges in insulin or some type of inflammatory event or infection. These are all stressful events.

All reproductive hormones can be compromised by stress. Merely replacing these hormones totally ignores the need to manage the adrenal glands and stress.

This is particularly important in peri-menopause (the transition into menopause) as these women count on adrenal function to give them the reserves that they need for hormones such as aldosterone, progesterone, estrone and estradiol. If their adrenals are healthy, they usually transition without much problem. But, if they have fatigued adrenal glands or the adrenals are in state of alarm due to stress, pregnenolone steal can cause shifts in these steroid hormones that are less than optimal.

Hormone Crèmes vs. Other Delivery Methods
Hormones crèmes have gained a great deal of popularity through several best-selling books that have touted their efficacy. However, there are major problems that have been discovered in using them. With this type of delivery method, the hormone is carried directly into the blood stream, bypassing the liver. Regardless of the dosage, the hormone levels build up, store in the tissue and at some point exceed the physiological range. The more body fat a person has, the more hormones they can potentially store.

As this occurs, a whole range of problems can develop as the hormone receptors down regulate, the endocrine system loses its feedback coordination and natural hormone production becomes impaired.

This buildup of hormone levels is best seen with free-fraction testing (and is usually missed in protein bound tests. We often see patients on hormone crèmes testing with levels 5 to 10 times greater than normal. Further, laboratory testing shows that it can take many months for levels to return to physiological states.

The preferred method of hormone delivery is sublingual drops. This method has several advantages. It still bypasses the liver like the crèmes do, but the sublingual hormone enters the lymphatic tissue and delivers more of the active hormone where it needs it be. With sublinguals, we also do not get the hormone buildup in the fatty tissue and the tendency to exceed the physiological range that crèmes give us.

Oral tablets, are another popular method of delivery, but also have disadvantages. Oral tablets are metabolized mostly in the liver, and this tends to tax the liver. Only about 10% of the hormone actually reaches the blood stream. With oral hormones, there is also the risk of conversion into other downstream metabolite hormones. For instance, if you take too much oral DHEA, it can potentially be converted, in the liver, into testosterone or estradial leading to imbalances that can have many unpleasant implications.

Sublingual hormones are clearly the preferred method of delivery. They tend to not tax the liver or buildup in the tissue. They are easy to take. They can be flavored to taste quite good. The only disadvantage to sublinguals is that the half-life of a sublingual hormone is about 8 hours, so it should be taken 2 to 3 times per day for optimal delivery.

Hormone Deficiency vs. Hormone Excess
What is the difference in the symptoms of hormone deficiency and hormone overload?

Interestingly, the symptoms are the same. The reason is that once you exceed a hormone’s physiological reference range for a long period of time, you cause the receptor sites to shut down. A great deal of the time, when people have symptoms of hormones deficiency, they are actually in a state of overload. In the standard health care model, these symptomatic patients are usually just loaded up with more hormones. They feel better for a brief period of time and then they crash again, because they are getting more receptor down-regulation. This goes on and on and they become a chronic (so-called) endocrine patient.

What these people really need is to clear these hormones out of their system. To do this, we use various formulas that support Phase I and Phase II liver detoxification. These generally include substances like: Milk Thistle, Dandelion root, Panax Ginseng, L-Glutathione, Glycine, N-Acetyl Cysteine, and DL-Methionine, along with B Vitamins, Magnesium, Zinc, Copper and Vitamin C. For elevations of testosterone or any of the estrogens, we also want to add methyl donors to support methylation pathways in the liver. These include: Vitamin B12, Folic Acid and Trimethylglycine.

As these hormones are cleared out, these patients can actually feel worse for several weeks. This occurs because as they begin to clear these hormones, their receptor sites need around two or four weeks to begin to regenerate. During this period, it is quite possible to see exaggerated symptoms, before signs of improvement.

Hot Flashes
It’s important to understand that hot flashes are not an estrogen deficiency syndrome. Rather, they are the result of estradiol spiking up and down. Clinically, we mostly see hot flashes in women going through the transition of perimenopause into menopause, as they begin to lose their ovarian sensitivity to FSH. Remember, the pituitary releases FSH and this causes the follicles of the ovaries to put out estradiol. As a woman loses this function, estradiol levels can wildly spike up and down.

We can decrease the impact of these fluctuations by using the selective estrogen receptor modulators that we spoke of earlier: Genistein, Daidzein, Black Cohosh and Dong Quoi. In addition, we can use the Tribulus, Maca, Panax Ginseng and Zinc to elevate FSH levels.

If the above compounds do not relieve the hot flashes within several months or if hot flashes are still occurring deeper into menopause (when we are no longer likely to see this estradiol spiking), it is possible that the mechanisms leading to them are caused by thyroid or adrenal dysfunction. Thyroid and adrenal hormones have some impact on thermal regulation. The thermal symptoms brought on by adrenal dysfunction are somewhat different than normal hot flashes. They usually involve sweating without the high levels of heat generated in normal hot flashes.

Osteoporosis
While much focus has been placed on balancing calcium levels in preventing and treating osteopenia and osteoporosis, when a woman has reached menopause, balancing hormone levels becomes a much more important factor than calcium. Calcium is important up until menopause because bone is still developing, but after menopause balancing hormones is the crucial factor.

A woman needs proper amounts of estrogen, progesterone and testosterone to maintain bone health. Also of importance for bone density are essential fatty acids. When estrogen levels drop, there is a shift in prostaglandins that create a state of inflammation that causes bone resorption. Increasing the amounts of good fatty acids in the diet and supplementing with high-quality, mercury-free fish and/or flax based oils is extremely beneficial to curb this inflammation and resultant bone loss.

Cortisol also has a major and largely unrecognized influence on bone loss. Cortisol elevations, if present, have to be managed.