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September 2003

Treating High Cholesterol by Replacing Hormones Lost to Aging
by Sergey A. Dzugan, Ph.D. & R. Arnold Smith, M.D.

Cholesterol is an important part of the story of blocked arteries (but it’s not the whole story!).
Cholesterol has an extraordinarily important function in an organism; it is the critical compound for life. It is the basic component of the cell membrane, bile acids, steroid hormones, and, in conjunction with sunlight, vitamin D3.

Neither cholesterol nor triglycerides can be dissolved in blood. They have to be wrapped up in a sphere known as a lipoprotein in order to transport them out of the intestine. In short, lipoproteins are the transport for insoluble cholesterol and triglycerides.

Low-density lipoproteins (LDL) carry cholesterol from the liver to different organs. Cholesterol is then absorbed by the cells around the body. Excess cholesterol is reabsorbed by the liver and reused or excreted into bile. LDL is known as “bad cholesterol” (even though “LDL” is not “cholesterol”).

High-density lipoproteins (HDL) are made in the intestine and the liver. They help to remove cholesterol from artery wall. HDL acts as a cholesterol mop, scavenging loose cholesterol and transporting it back to the liver. HDL is known as “good cholesterol” (even though “HDL” is not “cholesterol”).

Fig. 1

The human organism is in a state of dynamic equilibrium, know as homeostasis. One of the main roles in normal homeostasis belongs to multiple feedback loop mechanisms. Cholesterol is the precursor or the building block for the basic hormones: pregnenolone, DHEA, progesterone, estrogen, testosterone (Fig.1). Deterioration of the reproductive function, one of the most striking endocrine alterations occurring in aging, is related to a complex interplay of factors. Target organs may become less sensitive to their controlling hormone or may break them down at a slower rate. Hormone levels may change; some increasing, some decreasing and some remaining unchanged. Many of the diseases that middle-aged persons begin experiencing including depression, abdominal weight gain, prostate, breast and heart disease, are directly related to hormone imbalances. Conventional doctors are prescribing drugs to treat depression, elevated cholesterol, angina and other diseases that may be caused by hormone imbalance.

A few years ago we found out that some patients who had high cholesterol levels before hormonorestorative therapy (HT) were free of cholesterol problems during therapy. We started pondering as to why this had happened?

In our opinion, when the production of hormones starts to decline our body tries to correct this problem by increasing the production of cholesterol. A similar situation happens to women during pregnancy. When a female’s body needs more hormones for herself and her baby, cholesterol levels are elevated significantly.40-42 If a woman’s body is unable to increase the production of cholesterol the risk of an abortion and miscarriages is increased.43

Another situation is a low level of cholesterol. If your total cholesterol is less than 160, you have nothing to worry about. Wrong opinion! A low level of cholesterol means a low production of basic hormones (because of a limited amount of building blocks). Patients with a low level of hormones have life problems that include suicides, criminal behavior, depression, attention deficit disorder, cancer at young age, etc.44-49 Low cholesterol is a marker for poor underlying health.

When patients take cholesterol-lowering drugs (CLD) we can surmise that hormonal production will decrease. That’s why many patients on CLD have severe fatigue, fibromyalgia-like pain, depression, high risk of cancer, suicides, weight gain and impotency.50-52

Normally our body tries to keep a normal ratio between different hormones: DHEA/cortisol, estrogen/progesterone, female/male hormones. When we have a malfunction in a feedback loop mechanism we start to have the problems related to the imbalance of hormones (for example: male or female dominance, estrogen dominance, etc.).

Once again, when the production of hormones starts to decline, our body tries to correct the deficiency of hormones by the extra production of cholesterol. It looks like the elevation of total cholesterol serves as a compensatory mechanism for hormonal deficiency. Considering this, if we restore a youthful level of hormones there is no reason for the extra production of cholesterol. Hormonorestorative therapy may play a key role in “resetting” the various endocrine loops.

Formulation of new hypothesis
We suggested a new hypothesis, which we call the hormonodeficit hypothesis of hypercholesterolemia. This hypothesis implies that hypercholesterolemia is the reactive consequence of the age-related, enzyme-dependent down regulation of steroid hormone biosynthesis and their interconversion. In short, hypercholesterolemia is the compensatory mechanism for age-related decline of steroidal hormone production.

Basic understanding of our cholesterol metabolism can help with the process of restoring our body’s natural synchronization. Hormone supplementation can help bring our bodies back into balance.

Testing of the hypothesis
Forty-one patients ages 25 to 81 with hypercholesterolemia were treated between July 1997 and April 2003. Male to female ratio was 1:1.6 (16 to 25). All patients were treated by hormonorestorative therapy (HT) using anthropo (human)-identical hormones. This included a combination of several agents: oral pregnenolone and DHEA capsules and topical triestrogen, progesterone and testosterone gels. HT includes chemically identical molecules to human hormones and is administered in physiologic ratios with dose schedules intended to simulate natural human production cyclicity. We prefer to use the topical gels because they contain highly lipophilic molecules with low molecular weight, are very well absorbed through the skin, may use adipose tissue as a reservoir, and facilitate individualized dose prescription. Dose recommendations to patients during HT were individualized and were determined by serum hormonal levels during serial testing. That is why we did not use standard dose, rigid protocol or traditional design for this study. Doses were individually modified during HT to produce youthful physiologic (not “normal”) serum levels. We titrated doses to reach the laboratory defined hormonal blood levels of young adults between the age of 20 and 30 for both genders at which time a good level of all steroid hormones naturally occurs.

There are a few rules for HT: anthropo-identical structure of hormones, individually modified doses, cyclical manner and larger dose in the morning. Mono- or bi-hormonal therapy is usually inadequate. Poly (multi)-hormonal therapy is optimal. What we mean here is that all steroidal hormones should be properly replaced at the appropriate time of the day. If even one steroidal hormone is left out, then the body may respond to this deficiency by synthesizing more steroidal hormonal precursor, i.e. cholesterol.