General principles:

What are Bioidentical Hormones?

Much confusion exists about the term “bioidentical” . Often the public equates this term with “natural” “herbal “ or “botanical” remedies such as red clover or black cohosh, but this is not the case .

Bioidentical hormones are synthesized in a laboratory , often from plant sources such as yams, but are CHEMICALLY IDENTICAL to human hormones; as opposed to conventional medications for menopause ,in which equine or horse estrogens are used instead of human estrogens (eg Premarin – derived from PREgnant MARe’s urINe); and progesterone-like compounds – progestagens -(eg Provera – medroxyprogesterone acetate) -which are similar, BUT NOT CHEMICALLY IDENTICAL to, human progesterone.

Why is it important to make this distinction?

Because the whole controversy about administering HRT to menopausal women arose from a large trial called the WOMEN’S HEALTH INITIATIVE , which suggested that the use of combined HRT ( estrogen and progesterone) was associated with a small increase in the rate of breast cancer, and heart disease.

However the hormones used in this trial were oral PREMARIN and PROVERA (medroxyprogesterone acetate). Since then, this trial has  been criticized for not stratifying the risks according to age group, and a general conclusion reached that even the risks of administering these drugs increased with advancing years and were lower within 5 years of menopause.

Transdermal vs Oral Hormones

The principle  that transdermal estrogens are associated with significantly lower risks of *thromboembolic disease than oral estrogens, as is progesterone vs some synthetic progestagens- is widely accepted: *VTE/TED = blood clots leading to heart disease ,stroke, and pulmonary embolism  ESTER study “…Oral, but not transdermal, estrogen is associated with an increased VTE risk. …Micronized progesterone and pregnane derivatives appear safe with respect to thrombotic risk”.

What are the other advantages of using transdermal vs oral hormones ?

In simple terms, we can use lower doses, and produce less potentially harmful metabolites.

When we take any medication orally, it is first shunted directly from our small intestine to the liver, where most of the drug is broken down, or metabolized, into other compounds – metabolites- which are  excreted in the urine; this is called the enterohepatic circulation.

In the case of hormones, some of these metabolites can have potentially harmful effects – see section below on Estrone or E1 metabolites,some of which have a proliferative and potentially carcinogenic effect on breast tissue; and likewise for metabolites of some synthetic progestagens, which have a thrombogenic effect.

Also, the more oral drugs we are taking, the more potential for interactions between them, due to competition for the liver enzymes that  “detoxify” or break them down.

In contrast, when we apply a medication in a cream or gel formulation to our skin, it is absorbed directly into the small blood vessels (capillaries) bypassing the enterohepatic circulation;  smaller doses administered in this fashion are more effective than larger doses administered by mouth, by virtue of not being broken down in the liver (first pass effect). Smaller doses  have also less potential to cause unwanted  side effects.

Measuring levels of Hormones and their Metabolites

Logically, when we  are administering HRT ( Hormone Replacement Therapy) we should know which hormones are deficient and by how much, in order to administer the correct dose…and be aware that that dose will vary from person to person, depending on body size. metabolism, genetics etc. The old standard approach was to put everyone on the same dose of Premarin & Provera for menopause, and then wonder why there were problems !!

Hormones can be measured via blood , saliva or urine tests.

Blood and saliva tests are useful for measuring levels of hormones at a specific point in time -whereas urine testing is  used for checking metabolites, or the total production of a hormone over a 24hr period. This can be particularly useful for measuring hormones that are rapidly metabolized ,where blood levels will vary widely from minute to minute e.g. some adrenal hormones and Human Growth Factor.

When measuring blood levels of various hormones, we need to be aware of

Circadian production of certain hormones-  e.g. levels  vary according to  the time of day that the sample was taken e.g. testosterone and cortisol peak in the early am.

Monthly biorhythms e.g. female sex hormones typically follow a 28-day cycle.

Lastly we need to distinguish between total, free, and bioavailable  levels of the hormone; most hormones travel around the bloodstream bound to large carrier proteins (globulins), which cannot penetrate cell membranes to exert an active effect; a small proportion of the hormone is bound to smaller proteins, called albumen- and a smaller percentage still is unbound or free– these last two quotas can penetrate cell membranes, and are known collectively as bioavailable levels; what we are really interested in measuring is this fraction…however, this is often quite expensive to measure via blood tests, and not always available, through hospital labs.

A less expensive way of measuring bioavailable levels is salivary hormone testing:

In order to be detected in the  saliva, the hormone has first to enter the salivary gland cell- the biologically inert fraction of the total hormone level, i.e. that portion which is circulating in the bloodstream  bound to  large carrier proteins, is excluded from this measurement.

As well as being less expensive, and less stressful for the individual that blood tests, salivary testing allows the collection of hormone samples in the early morning and late evening, so as to better understand  circadian rhythms– which is important in evaluating adrenal and pineal gland function- e.g. cortisol and melatonin levels.

The Hormonal Symphony: it’s all about Balance

Hormones secreted by different glands do not work in complete isolation from each other- there are  interactions and interdependent relationships between different systems – by competition for receptor sites, or competition for synthesis along common metabolic pathways.

e.g. A relative  excess of estrogen in the perimenopausal years may oppose the action of thyroid hormones leading to what is known as a functional hypothyroidism – i.e. symptoms of low thyroid activity, despite normal levels of thyroid hormones; or chronic psychological stress can suppress production of sex hormones – as both cortisol (the stress hormone) and testosterone share common precursor compounds.

Some hormones are at opposite ends of circadian rhythms- e.g. cortisol and melatonin are at opposite ends of the sleep-wake cycle; high cortisol secretion at night will suppress melatonin secretion which in turn , can have long term consequences on immune status and overall health (an important phenomenon in shift workers). Poor sleep will affect HGH (growth hormone) production, which in turn , will affect body composition; and weight gain around the middle can lead to insulin resistance etc.

These are only some illustrations of the complexity of the hormonal symphony; as Newton would have put it ..” For every action, there is an equal and opposite reaction..” hence the emphasis in metabolic medicine is  on detecting and correcting hormonal imbalances.

Let’s look at some common scenarios resulting from hormonal  imbalances