Are Bio-identical Hormones Safe?

Are Bio-identical Hormones Safe?

by Ron Hunninghake, MD

When I was a young teenager, it never crossed my mind that I and my fellow adolescents had extremely high hormone levels. Then . . . and now, no doctor, parent, high school athletic coach, or girlfriend/boyfriend would question the safety of my hormones.

We did not get “hormone-related cancer.” At worst, we suffered from some testosterone-related acne and hormonal over-impetuosity. Ah . . . wouldn’t it be great to have some of that pubescent energy back again! I could eat a lot and still maintain a muscular physique. Hormones were definitely a “good thing.” Too bad, as commented on by Mark Twain, that “youth is so wasted on the young!”

Now, as many of us enter our elder years we hear about HRT, or Hormone Replacement Therapy. We hear great stories of restored healthiness and wonder if this approach could give us back some of that lost vim and vigor of our youth.

Yet, many elders have an uneasy fear of hormonal therapy. The big “C” word lurks directly behind what conventional doctors consider the risky promise of hormone replacement. This fear haunts the menopausal female (fear of breast cancer from estrogen replacement therapy) and to a lesser degree the andropausal male (fear of prostate cancer from testosterone “low T” therapy).

The medical rationale for hormone replacement is not unreasonable. Doctors give thyroid when the thyroid gland fails. Insulin is “replaced” in Type 1 or advanced Type 2 diabetes. Addison’s disease occurs when the adrenal glands stop working, thus giving rise to the need for cortisol—a life saving hormone for that condition. Testing for vitamin D has become commonplace. D3 is a hormone-like vitamin, the deficiency of which can cause many degenerative conditions which can be prevented with “vitamin D3 replacement therapy.”

In this brief article I would like to shed light on what appears to be a blatant incongruity: how can something that is so life enhancing in our youth be so potentially  dangerous in our elder years. How can hormone replacement, which is practiced in many other areas of medicine, turn sinister when the sex hormones are replaced in aging women and men?


What happens to many women when their ovaries stop producing estrogen and progesterone? Menstruation stops, of course. Hot flashes, night sweats, sleep disturbance, vaginal atrophy, mood and memory dysfunction, accelerated heart disease, osteoporosis, macular degeneration, colon cancer, arthritis, and more rapid skin, hair loss and nail deterioration occurs. Granted, these manifestations of menopause do not occur in every woman, or occur only mildly, resolving over time thanks to their adrenal glands “taking over” and producing the menopausal estrogen—estrone. So some women handle “the change” quite well. For many others, it can be devastating.

Men too can suffer from a male climacteric, though the changes are often more subtle and slower to develop. Loss of muscle mass, lower motivation and libido, depressed mood, altered sleep, nocturnal urinary frequency, belly fat, insulin resistance and cholesterol elevation (with increasing cardiovascular risk) are possible manifestations of an overall loss of “quality of life.’ “I’m just getting old and over-the-hill” is the thought process that often accompanies diminishing male testosterone levels. (Women can suffer from loss of testosterone as well.)

The use of testosterone for male andropause is a more recent phenomenon. However, the use of HRT for women had been an established medical standard for decades. Why? HRT helped to attenuate the well known phenomenon of a women’s increased risk for heart disease with the onset of menopause. It is well established that cardiovascular disease is by far the #1 killer of menopausal women. All the major HRT observational studies showed a relative reduction in heart disease in women taking estrogen. This is the “heart protective” effect of estrogen at work.

One major exception to this research finding now exists that drastically changed that “standard of care.” This one highly publicized study changed the course of medical care for menopausal women everywhere. Because of this study, doctors and their female patients silently hold a great fear of breast cancer whenever the topic of HRT is mentioned. How could just one study be so influential?


The Women’s Health Initiative (WHI) was a large NIH sponsored hormone study of 27,000 women begun in 1993 that was prematurely terminated when a surprising increase in breast cancer and heart disease showed up in 2.5% of the enrollees. Suddenly, doctors everywhere began pulling their female patients off of the Premarin and Prempro hormones that were used as the replacement hormones in the WHI women.

I would like to make three cogent comments on WHI that are believed to be responsible for the change of standards and the mainly negative bias and fear surrounding the modern use of HRT:

1) The average age at time of enrollment in WHI was 63. The increased cardiac risk that did occur was in the 1st year of treatment which then greatly diminished in subjects remaining in the study. The younger enrollees (ages 50–59) experienced reduced cardiovascular risk. (Their relative risk ratio was 0.56 compared to controls.) This strongly suggests that the older enrollees already had emerging cardiovascular disease that could not be attenuated by the “too late” estrogen replacement.

2) The Prempro hormone used in the WHI is part Premarin and part Provera. Premarin is derived from pregnant horse urine (equine estrogen) and Provera is a synthetic progestin, a patented alteration of native progesterone. These two molecules are clearly NOT “bio-identical” female sex hormones. Furthermore, progestin added to estrogen is a known cause in both animal and human studies of increased breast cancer.

3) Finally, these NON-bio-identical hormones were given by the oral route. This invites “first pass” changes by the liver with multiple adverse consequences which added to the negative results in WHI:

a. increased SHBG (sex hormone binding globulin) with resultant decreases in the protective availability of the hormones at the cellular level

b. increased clotting enzymes with increased risk of stroke and thrombosis risk

c. increased gallbladder disease (similar to what occurs with birth control pills)

d. increased triglyceride levels which is associated with increased numbers of the small/ dense, more atherogenic LDL particles in individuals who consume too much sugar/high glycemic carbs


While the majority of doctors and researchers came to the conclusion that HRT was unsafe, many alert medical practitioners realized that the findings of WHI pointed to a need to “clean up” the methodology of HRT. The following changes in the way sex hormones are prescribed and monitored suggests a safer and more effective HRT is available to women (and men) who understand that nothing in this world is “risk free,” but that through the use of better standards of care, these risks can be lowered so that the benefits of HRT can be realized in those individuals who truly need it.

1) Use hormones that are exact chemical replicas of what is produced by the body.(Bio identical hormones are NOT “natural” in the strict sense. They are synthetically converted sterols from yams and soy that are converted in the lab to biologically identical molecules.)

2) Start replacement therapy as near to menopause (or andropause) as is reasonably possible before the hormonal deficiency creates adverse degenerative changes in the patient.

3) Use a route of absorption besides oral (apply topically to either skin, vaginal mucosa, buccal mucosa using troches, or even anal mucosa in men.)

4) Carefully monitor blood levels after initiation of therapy to ensure that the hormonal levels remain in the same, safe physiologic range as was existing in the body prior to “the change.”


These new standards of a more ideal hormonal replacement methodology reflect key orthomolecular principles first elucidated by Nobel Laureate Dr. Linus Pauling in his 1968 article in Science. Keep in mind that “ortho” is a prefix that means “right” or “correct.”

a. The right molecule: using molecules that naturally occur in the body and are essential to healthy biochemical and cellular processes. The lack of these molecules create deficiency diseases.

b. The right dose: using dosages of these ortho-molecules that actually correct dys-regulated or diseased conditions within the body (rather than simply suppressing symptoms of the condition) .

c. The right dosing: using dosages of the ortho-molecules that reflect appropriate physiologic timing, route of entry, and optimal metabolic processing and elimination pathways.

d. The right professional usage: using ortho-molecules appropriately to correct specific
conditions in unique individuals based upon careful clinical selection, laboratory testing,
and the professional training and experience of the practitioner, with special emphasis on
the balance of safety and effectiveness for each patient seeking this kind of medical care.

Please note that “orthomolecular” includes synthetically produced molecules such as synthetic vitamin C. Bio-identical hormones are synthetically made in a way that produces molecules that precisely match what is normally present in the human body.

It would be impractical, overly expensive, and aesthetically untenable to attempt to obtain enough human urine to extract “natural” hormones for use in every human seeking treatment. It is, however, of historical interest that in the middle ages the Chinese collected the urine of young people, evaporated it in the sun, and then gave the resulting residue to the elderly with impressive healing results. This was mankind’s first foray into HRT!


Breast cancer in women is on the rise in modern times. This may be a reflection of earlier detection due to screening or it could be due to epigenetic factors that increase risk. What are these risk factors?

One way of determining the risk of developing breast cancer is to look at a simple comparison between an experimental group and a control group, where the experimental group reflects a behavior (such as alcohol usage), an “event”, or some other independent factor. Relative risk (RR)is expressed according the following definition:A relative risk of 1 means there is no difference in risk between the two groups.

RR of < 1 —the event is less likely to occur in the experimental group than in the control group.
RR of > 1 —the event is more likely to occur in the experimental group than in the control group.
While gender, age, and family history are major risk factors for breast cancer, the following chart shows several additional risk factors that need to be factored into any risk assessment:

Experiment Group                                                          Relative Risk
WHI Study users of Prempro                                        1.26
Greater than 13 years of education                              1.79
Greater than 14 alcoholic drinks per week                  1.70
Body Mass Index exceeding 30.7 kg/m                       1.60
Left handedness                                                               1.42
Nulliparity (never pregnant)                                          1.40
Night shift worker                                                            1.36
Composite risk calc. from 39 studies of ERT users     1.20

To see how these Relative Risks affect your Absolute Risk, use the following chart to multiply anyone of the Relative Risks times the percentage of your Absolute Risk to see how this “event” or characteristic affects your current Absolute Risk.

Age Category            Absolute Risk            Percentage

30-39                         1 in 233                      0.43%

40-49                         1 in 69                         1.4%

50-59                         1 in 38                         2.6%

60-69                         1 in 27                          3.7%

70+                             1 in 8                            12%


There is no absolute way to escape the risk of breast cancer. Absolute safety does not exist. The use of estrogen in replacement therapy as a Relative Risk factor does have a minor additional risk associated with it. But if used according to orthomolecular principles, this minor risk may be attenuated with the attending benefits of a greater quality of life, less heart disease, less bone disease, better sleep, mood, cognition, and a host of youthful characteristics we cherish as normally being reserved only for “the young.”