Menopause - The Dance of The Steroids

Excerpted from
What Your Doctor May Not Tell You About Menopause : The Breakthrough Book on Natural Hormone Balance
By John R. Lee, M.D., Virginia Hopkins

The word steroids may conjure up visions of muscle-bound bodybuilders and unpleasant side effects, but steroid is really a generic name for dozens of body regulators (hormones) made from cholesterol. Cholesterol, the basic building block for the steroid hormones, gives them all a similar structure. An analogy would be a basic clothing ensemble. You begin with a beige jacket and matching slacks. Add a blouse, a necklace, and some pumps and you have a business outfit for a corporate office. Make it black and add a scoop-neck silk blouse, cut the jacket at the waist, and you're ready for a night on the town. Or make the jacket and slacks navy blue, add a button-down shirt, some epaulets and gold braid, and you have a military uniform. The basic suit stays the same, but the additions, subtractions, and other alterations make the difference in the role you play. In the same sense, all the steroid molecules resemble cholesterol in their basic structure. Switch a few atoms around and the role of the hormone can change dramatically.

Without sufficient cholesterol, we can't make sufficient steroid hormones. (If you would like to see how biochemists picture the cholesterol molecule, turn to the appendix.) Some of the other more familiar steroids are estrogen, progesterone, testosterone, the corticosteroids, and dehydroepiandrosterone (DHEA). The steroid drugs that bodybuilders use are called anabolic steroids. Anabolic means that they have a "building" function rather than a "taking apart" function. Testosterone, for example, helps build up muscle mass, as do some other androgens (male hormones). Although the workings of the steroids are subtle and complex, a slight imbalance can have major effects. Learning a bit about steroid hormones can give you an enormous advantage in making informed decisions about hormone replacement therapy. What I am about to tell you here, most doctors forgot a long time ago, but the information is fundamental to truly understanding hormone balance.

The first step in the body's manufacture of steroid hormones from cholesterol happens in tiny energy packets called mitochondria found within every cell of the body except red blood cells. From cholesterol, the mitochondria make a hormone called pregnenolone, which can then be transformed into progesterone or 17-OH-prcgnenolonc. Then, from these two steroids, progesterone and 17-OH-pregnenolone, all the other steroid hormones can be made by relatively minor molecular modifications, depending on body need. In this sort of production, one steroid is transformed into another. Many of the steps along the steroid pathway are active hormones in their own right even though they also serve by being transformed into yet other hormones.

Although the steroid hormones are remarkably similar in shape, each of them has markedly different effects, and these differences arise from very slight variations in their molecular structure. Let's look at some of the major players in this constantly shifting milieu of steroid hormones.

Choreographing the Dance

The steroid hormones shown in Figure 2 are made primarily in the ovaries of women, the testes of men, and the adrenal glands of both sexes. As far as we know, all of the steroid hormones are made from cholesterol. This is one of the reasons it is so important not to go on a no-fat or nocholesterol diet. Although our body can manufacture about 75 percent of our cholesterol from other foods we eat, the remaining 25 percent comes directly from cholesterol-containing foods. Eliminate cholesterol entirely and hormone imbalance may result. Low cholesterol in the elderly has been linked to depression and suicide. As in most things, moderation and balance are the answer. The transformation from one hormone to another requires enzymes, which in turn require vitamin and mineral cofactors. A substance that is the source of another substance is called the precursor.

The Journey Along the Steroid Hormone Pathway

As I describe the pathways in words, follow my description on the diagram in Figure 2.

The journey begins on the upper left corner with pregnenolone having been derived from cholesterol. The flow of hormones then progresses from pregnenolone along one of two major pathways: one to the left and down through the adrenal DHEA pathway, or straight down through progesterone in both the ovarian and adrenal glands. Both pathways lead to what we call metabolic end points. Aldosterone, Cortisol, and the estrogens are the final stops, or metabolic end points, on the steroid hormone pathways.

With the exception of the end point hormones, all of the steroid hormone molecules are capable of being converted into some other molecule. Testosterone, for instance, can be a precursor of the estrogen called estradiol, and androstenedione can be a precursor of either testosterone or estrone, another estrogen. Estrone and estradiol can be interchanged into each other via a redox (reduction/oxidation) system in the liver. Progesterone is a precursor in several pathways, one leading to androstenedione and on to the estrogens and to testosterone, another to Cortisol, and another to corticosterone and aldosterone. Similarly, DHEA is a precursor in the pathway leading to testosterone and androstenedione, the latter leading on to the estrogens but not to other corticosteroids.