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GuardedlyOptimistic

A Really Good Article on Female Androgen Problems

http://www.infertilityphysician.com/androgen/intro.html

Androgen Disorders in Men and Women

INCLUDING

THE INSULIN RESISTANCE -

POLY-CYSTIC OVARY SYNDROME

Menopause is the most common endocrine disease in women. All women will eventually experience it.

Androgen problems constitute the most common endocrine disorder in women of reproductive age (puberty to menopause). Poly-Cystic Ovary Syndrome and its many variants is the most common reason for excess androgen production. A great deal of confusion exists concerning these problems not only among the women who suffer them but also the treating physicians as well. The purpose of this pamphlet is to explain this confused area of endocrinology to provide you with a better understanding of the problem you have and the therapy employed.

"Androgen" is the overall term applied to any hormone that produces male characteristics. In this way, it is similar to the term "estrogen" which describes any hormone producing female traits.

Men and women both produce androgen - obviously men are producing more androgen but even normal women produce some androgen.

There are certain physical characteristics that we associate with maleness. These include a beard, large muscles, acne, a deep voice, baldness and enlargement of the Adam's apple. Men have these characteristics not because they are genetically programmed to develop them but because the male endocrine system produces far more androgen than the female endocrine system.

In order to understand what is happening, it is necessary to define certain terms that you may come across in your readings.

As indicated, "androgen" is the term used for any hormone or substance that creates male-like symptoms or physical changes.

"Estrogen" refers to any hormone or substance that confers female symptoms or characteristics.

It is important to understand that everyone, both men and women, have hair over their entire bodies. The only exceptions are the palms of the hands and the soles of the feet.

There are two main types of hair - "vellus" and "terminal".

Vellus hair is finely textured. It may be light or dark in color depending upon the characteristics of the individual. It is not the color of the hair that makes it "vellus" - it is the thickness and texture of the hair.

As a result, darkly complected women will have dark hair on their face, arms, legs, abdomen and back; whereas a blonde woman will have lightly colored hair.

Terminal hair is coarse and thick. Again, it is not the color of the hair per se, but the texture that is important. However, all other things being equal, terminal hair is almost always darker than the vellus hair on any given individual.

All women have vellus hair on their face. It is therefore critically important to understand that increased androgens in a woman does not cause hair to grow. The increased androgen converts vellus into terminal hair - the same process that normally occurs in a boy at puberty.

It is therefore critically important to understand that any hormone therapy will not eliminate the hair. The purpose of hormone therapy is first to slow the growth of new hair and then to ultimately reduce the hair altogether. Permanent removal requires physical elimination of the hair either by electrolysis or one of the new laser technologies. Treatment requires a combination of both a hormonal and a physical approach.

Hirsutism is defined as the growth of terminal hair (i.e. androgen stimulated hair) in women in places where it normally does not occur. Such places include the chin, neck, the skin over the upper breasts (not around the nipples), the skin over the breastbone between the breasts, and the lower abdomen.

A term you may frequently encounter is "idiopathic hirsutism". Idiopathic means unknown or unexplained. As will be discussed later in this pamphlet, much confusion has arisen because women who were evaluated for androgen disorders were often found to have normal serum levels for the various hormones. It was therefore - incorrectly - concluded that because the hormone levels in the blood were normal, there was no underlying hormone problem. We now know that this is incorrect and there is no place for the term "idiopathic hirsutism". A reason for the hirsutism exists and can usually be found in almost every woman.

The term "hirsutism" itself simply refers to the presence of terminal hair (i.e. androgen stimulated hair) on a woman in locations where it simply does not belong. However, the presence of terminal hair in all locations does not necessarily convey the same significance. The general rule is that hair in the mid-line of the body is more important than hair farther away. For instance, hair on the breasts around the nipples is fairly common and by itself has no endocrine significance. However, hair between the breasts, over the sternum (breast bone), is very significant.

Again, hair on the chin and neck is important; hair in front of the ears (like side-burns) is less significant - especially if that is the only location.

Many women, particularly women with darker complexions, are very distressed because they begin to grow a mustache. Again, the presence of hair on the upper lip is normal - it is supposed to be there. However, if the woman is dark, her hair will be dark and although it is often unsightly, by itself, a mustache usually has no endocrine significance if the woman does not have hirsutism elsewhere on her body. Under such circumstances, the best therapy is simply to bleach.

Some women, especially if darkly complected, have significantly more prominent and darker body hair. However, so long as the hair is vellus (which is usually is), it is normal though it may be unsightly. Such "excess" hair (it really isn't) is termed hypertrichosis. Unfortunately, there is no treatment. The hair is supposed to be there and it is darker for hereditary, not hormonal, reasons.

All women produce some androgen in the same way that all men produce some estrogen. To a great degree, the differences between men and women is more a quantitative rather than a qualitative difference. Therefore, women will develop "male" characteristics if their androgen production is increased for whatever reason. Since increased androgen production in women is a very common problem, the treatment of such disorders constitutes a very large part of my practice.

It is also becoming apparent that some men may produce too much male hormone and this may play a significant role in infertility. It may also be of importance in men with severe acne. Early balding (before age 30) is often a sign of an androgen disorder in men, especially if that man has any female relatives with Poly-Cystic Ovary Syndrome.

There are many hormones that are classified under the overall heading of androgen. There are two principal biologically active androgens - Testosterone and Di-Hydrotestosterone or DHT. Testosterone is produced directly by the ovary, the testicle and the adrenals.

DHT is produced by the conversion of testosterone by an enzyme called 5-alpha-reductase. In addition, the ovaries and adrenals produce another hormone - androstenedione - which can be easily converted to testosterone. Lastly, the adrenals produce an additional hormone, DHEA. DHEA has a very short biological "life" but the body converts it into a much longer lasting hormone, DHEA-S. DHEA is, unfortunately, sold over-the-counter in drug stores. The manufacturers are able to get away with this because they have slipped it past the FDA by calling it a nutritional supplement, even though it is a very powerful hormone with potentially serious side effects.

The same is true for androstenedione. It too is sold over the counter as a "nutritional supplement" but is in fact a very powerful hormone with potentially dangerous side effects. It should not be available without a prescription and proper monitoring.

These other hormones, especially DHEA, are easily converted to testosterone. Much of the conversion of these other hormones to testosterone takes place in the body fat. It is for this reason that obese women commonly show evidence of increased androgen production. Overweight women have elevated serum androgen levels even they do not have significant acne or hirsutism.

While the names of these hormones are not words you would tend to use at a cocktail party, you may see them on a bill from a lab or in a letter or report or on the Internet and I wanted you to at least know what they are. Furthermore, DHEA is now sold over the counter in drug stores and health food stores. Many people are taking it, and there is the potential for significant problems as your body will convert DHEA into more potent androgens very easily. This will result in increased androgen levels in your blood, resulting in hirsutism, acne, elevated total cholesterol, increased LDL cholesterol (the bad one) and decreased HDL cholesterol (the good one). DHEA should never have been allowed to be sold without prescription and I would caution you not to take it without careful supervision.

The source of androgen production in both men and women is principally the adrenal gland and the gonad (either the ovary or the testicle). Men produce approximately 10 times as much testosterone per day as women and the serum concentration of testosterone in men is 10-20 times that of women. This accounts for the fact that men have all the manifestations of androgen - namely hair on the face, increased dark body hair, deepening of the voice, larger muscles and, in later years, thinning of the hair or baldness.

It is important to understand that women will develop symptoms of increased androgen production if they also produce too much androgen. It is also important to understand that the total daily production of testosterone is the critical factor. The amount of androgen produced each day may be increased but because of how the body functions, the actual concentration of the male hormones in the blood may not rise. Failure to understand this fact is what causes much of the confusion surrounding androgen disorders.

After a hormone is produced, either directly or indirectly, it travels through the bloodstream to the various parts of the body. The hormone then leaves the bloodstream where it acts on its target organ such as the hair follicle. The hormone then is metabolized, usually by the liver, after which it is excreted in the urine.

When a woman produces too much androgen, it is fairly easy to suspect that she has a hormone problem. The symptoms of increased androgen production in women include menstrual irregularity often proceeding to a complete cessation of menstrual periods, hirsutism, acne, obesity and often infertility. While actual baldness in women, particularly younger women, is uncommon, thinning of the hair in younger women may also be an indicator of this particular type of hormone problem.

The amount of hormone produced by the body on a given day is called the "production rate". The amount of hormone removed from the bloodstream, metabolized and then excreted is called the "clearance rate". Therefore, you can readily appreciate that the concentration of a hormone in the bloodstream is simply the difference between the production rate putting the hormone into the blood and the clearance rate which is removing the hormone from the blood. This is an important concept to understand.

One of the most important things to understand about androgen disorders is that if a woman shows clinical evidence of increased androgen production, she is indeed making too much androgen. In other words, the production rate of androgen is increased. However, it is also true that through mechanisms that we do not fully understand, androgens have the ability in influence and control their clearance rate. When the production rate of androgen is increased, the clearance rate is also frequently increased. In other words, the faster the body is making it, the faster the body is getting rid of it. Therefore, in a situation such as this, the levels of the hormones in the bloodstream will remain normal or perhaps only slightly elevated.

Failure to understand this has caused people to state that if a woman has hirsutism but normal serum androgen levels, she has "idiopathic" hirsutism, incorrectly believing that the normal hormone levels rule out a hormone problem. WRONG! This is why there is no such entity as idiopathic hirsutism. A woman with hirsutism has a hormone problem.

Increased androgen production in both men and women is often due to increased androgen production from the adrenal as a result of an underlying enzyme deficiency or from the ovary in women who do not ovulate. In many women, both the ovary and the adrenal play a significant role along with body fat in women who are overweight.

Another source of increased androgen production is the increased conversion of testosterone to DHT by the 5-alpha-reductase enzyme. This conversion occurs in the hair follicle itself. DHT is the principal androgen acting on the hair follicle. It is now recognized that some women have evidence of increased androgen effect because of increased 5-alpha-reductase activity even though there may not be an increase in their total daily androgen production. They are still making too much androgen but it is a localized increase at the level of the follicle rather than a generalized increase in total body androgen production.

Rarely, a tumor of the ovary or the adrenal may produce too much androgen. These tumors are almost always benign, they are usually quite small and they are very uncommon. However, they produce large amounts of male hormone. When these tumors occur in women, they do much more than cause irregular menses, acne, hirsutism and infertility. These tumors will actually virilize a woman - in other words, she will develop male characteristics such as a deeper voice, male pattern baldness, increased muscle mass, a male body contour, etc. The presence of these tumors can be suspected by either the symptoms the woman comes in with or the level of male hormones in the blood.

Women with evidence of increased androgen production exhibit symptoms that are classified into 2 main categories - those that we term "defeminizing" and those that we term "virilizing". Defeminizing symptoms are much, much more common and are usually the result of an overproduction of androgen by the ovaries and/or adrenals due to an alteration in the basic normal functioning of these glands. Defeminizing symptoms include menstrual abnormalities, acne, hirsutism and infertility.

Virilization means that the woman is taking on definite male characteristics. This implies a much higher level of androgen production and virilization usually means the presence of an androgen-producing tumor although it can be seen in cases of severe PCOS (see the section on PCOS later in this pamphlet. These tumors are almost always, however, benign. Virilizing symptoms include complete cessation of menstrual periods, deepening of the voice, baldness and enlargement of the muscles. Enlargement of the Adam's apple and enlargement of the clitoris are also seen.

The underlying abnormality that creates these problems is somewhat complex but I believe that it is critically important for you to understand what is going on for several reasons. First of all, as will become apparent, these problems are inherited. Understanding them may help other members of your family to obtain help and successful treatment for their problem and it may alert you to the fact that indeed your whole family has had a problem for several generations that no one diagnosed. It also has some implications in terms of the children that you may have someday. Lastly, the therapy may require lifelong hormonal treatment to control the problem. It is, therefore, of critical importance that you understand exactly what is going on, why the tests are necessary to diagnose the problem and what the implications are for the future.

THE PATHOPHYSIOLOGY OF ANDROGEN DISORDERS

Although it doesn't have to be, the evaluation and treatment of a woman with an androgen problem is perceived by many to be a very complex issue. It certainly can be confusing. One of the principal reasons for this is similar to the parable of the three blind men who had hold of an elephant. One blind man was holding the elephant's tail; another was holding its trunk; the third was holding its leg. Each described the elephant based upon the part that he was holding - none of them could step back and see the animal in its entirety.

Similar problems have resulted when trying to evaluate androgen problems in women. There are three principal sources of excess androgen production in women - the ovary, the adrenal, and her body fat. Depending upon a researcher's particular interest, one of these areas might be studied intensively to the exclusion of the others. Furthermore, until relatively recently, it was not fully appreciated how complex an interaction there actually is between these three segments. Although there has been a great deal of research done over many many years, a few pieces of the puzzle have finally fallen into place - pieces which go a long way in explaining the nature of this problem.

The term "physiology" refers to the normal functioning of a particular body organ or system. The term "pathophysiology" refers to the abnormal functioning of a particular body system which ultimately leads to disease. By explaining to you the pathophysiology of androgen disorders, I hope that you will understand better the tests that are involved, how to interpret those tests, and how the treatments are designed to correct the abnormalities.

All women produce some androgen. The term androgen itself refers to any hormone that either directly by itself or indirectly by conversion to other hormones produces changes that are classically associated with maleness. The degree to which these changes occur depends on many complex interacting factors but the most important is the actual amount of excess androgen that is being produced. The more androgen your body is making, the more severe the changes will be. However, genetic factors also play a significant role. Oriental women may show no excess facial hair whereas women of southern European extraction may have a considerable amount of hair for relative small increases in testosterone.

The principal biologically active androgen is testosterone. This is the name with which most people are familiar.

In certain body systems, particularly in the hair follicle, testosterone is converted to another hormone - dihydrotestosterone. In the hair follicle, it is dihydrotestosterone that is the active hormone.

Various other hormones are in and of themselves not biologically active. However, the body has the ability to transform these hormones into testosterone - either directly or indirectly. They, therefore, contribute to the overall body's level of androgen.

The principal androgen of the ovary is androstenedione.

The principal androgen of the adrenal is Dehydroepiandrosterone (DHEA). The adrenal gland produces different amounts of its various hormones at different times of the day. Therefore, the concentration of DHEA in your blood stream depends upon the time of day it was drawn. However, the body adds a sulfate molecule to DHEA, creating a substance called Dehydroepiandrosterone Sulfate or DHEAS, sometimes abbreviated DS. The concentration of DHEAS in your blood stream is fairly constant throughout the day. This is the hormone that is usually measured since it does not show any time dependent variation and the levels can be checked at anytime the woman happens to be in the office.

There is another hormone that you may see mentioned frequently. Its name is "17 alpha hydroxyprogesterone". Although it is not an androgen, it is an important intermediary step in the production of androgens and an elevated level is a marker for a somewhat common adrenal problem. More about that later.

There are a couple of other hormones that will be mentioned here simply because you may come across them in your reading. These two "hormones" are 11-desoxycortisol and 17- hydroxypregnenelone. Again, these hormones are intermediaries. They do have clinical significance but the number of patients in whom they would be important is very very small, particularly in an adult population.

It is important to understand that a normal functioning ovary and adrenal produces androgen. When these organs are functioning abnormally, they produce excess amounts of androgen and this leads to the various clinical syndromes.

One of the principal functions, if not the principal function, of the ovary is to produce an egg each month. The ovary does this in a structure called the follicle which has several layers of cells - each with a different function.

The outermost layer of the follicular cells produces androstenedione which the inner layer then converts to estradiol - the principal estrogen produced by the ovary in a premenopausal woman. Anything that disrupts the normal ovulation process leads to increased androstenedione production by the ovary. It may also lead to increased testosterone production as well.

One of the principal functions - again, perhaps the principal function - of the adrenal gland is to produce cortisol. DHEA is an intermediary step in the production of cortisol. Again, anything that disrupts this normal sequence of events will lead to an increased production of DHEA. Many years ago, a few articles were published that showed that abnormal ovarian function would also lead to increased DHEA production. However, the data was scant and not well substantiated. Newer, better done studies now clearly show that the type of abnormal functioning that you almost always see in women with Poly-Cystic Ovary Syndrome (PCOS) leads to increased adrenal production of DHEA and when you control the ovarian abnormality, the DHEA levels will drop.

Insulin resistance leading to increased insulin production is known to stimulate ovarian androgen production. There is now some evidence that insulin also stimulates adrenal androgen production. Insulin is emerging as the main culprit in PCOS and related syndromes.

Adrenal abnormalities produce a number of clinical syndromes that are often indistinguishable from PCOS. Although at one time it was felt that these syndromes were common, we are now beginning to realize that purely adrenal abnormalities are less common. Much of the confusion developed because of our incomplete understanding as to how much altered ovarian function affected the way the adrenal gland produces its hormones.

THE ADRENAL GLAND AND ITS HORMONES

There are many endocrine glands in the body. One of the most important and one of concern in women with hirsutism or other androgen problems is the adrenal gland. Primary adrenal abnormalities do exist. At one time, before we had a better understanding of the problem, it was felt that primary adrenal abnormalities were more common than they are. Now, we have come to realize that for most women, they have PCOS which leads to abnormal adrenal function.

Your body has two adrenal glands - they are about the size of your thumb and they are found just above the kidneys.

The outer portion of the adrenal gland is called the adrenal cortex and the inner portion is called the medulla. For those of you who are interested in these things, the adrenal medulla is the site of epinephrine (adrenaline) production.

The adrenal cortex has three zones - outer, middle and inner. Although the same types of reactions take place in all three zones, the outer zone is concerned predominantly with the production of a hormone called aldosterone which controls your body's salt and water balance.

The middle layer of the adrenal cortex produces cortisol.

The inner layer of the adrenal cortex produces androgen.

The adrenal gland produces its various hormones (which are all quite similar to each other in terms of their biochemical structure) through a series of steps starting with cholesterol. Each step is very carefully and specifically controlled by a separate and distinct enzyme. Defects or abnormalities in any one of these enzymes means that the chemical change that it (the enzyme) controls does not take place properly (or may not take place at all).

When this occurs, the orderly progression from cholesterol to the various adrenal hormones is disrupted and the adrenal gland is not able to function properly. Even though the adrenal gland makes three distinct groups of hormones, the only one that is of critical importance for your life and health is cortisol and it is the regulation of cortisol production that determines the overall level of activity of the adrenal gland. This is an extremely important fact to keep in mind because it is the driving force behind many of the abnormalities in the adrenal gland that bring women into my office. It is especially important in pediatric endocrinology, particularly in babies born with "ambiguous genitalia" - i.e., babies whose genitals at birth are not normal and it may be impossible to determine whether the baby is a boy or a girl.

The adrenal gland has to make a certain amount of cortisol each day. Your life, health and well being depends upon it. If the adrenal gland is unable to do this, mechanisms are set in motion to insure that adequate cortisol production occurs even if it means that other hormones may not be produced in normal amounts. In fact, they are often produced in excess amounts.

Think of the pathways within the adrenal glands for the production of the various hormones as if there were three parallel roads all going in the same direction with a series of bridges in each road and, furthermore, with a series of crossroads that link the three main roads.

Think of one of the enzyme deficiencies in the adrenal cortex as if one of the bridges on one of the roads was either completely gone (a complete enzyme defect) or the bridge was under repair and reduced to one lane only (a partial defect).

If you were traveling on one of the roads, and the bridge ahead of you was not carrying its full load, you would take one of the crossroads over to another main road to complete your journey. This is exactly what happens in the adrenal cortex. If one of the enzymes that controls cortisol production is either absent or defective, hormone synthesis in the adrenal gland is shifted into other pathways. Depending upon the nature of the enzyme defect and the degree to which the enzyme is defective, certain hormones will be produced in excessive amounts and other hormones will be produced in much lesser amounts than they ought to be.

ADRENAL ENZYME DEFICIENCIES AND ANDROGEN DISORDERS

Five principal adrenal enzyme abnormalities have been described. The most serious involves an absence of the enzyme that allows the adrenal gland to begin the conversion of cholesterol to the other hormones. With this deficiency, the most serious, no adrenal hormones can be produced and these babies will die almost immediately after birth. If the appropriate diagnosis can be made, it is possible to anticipate the problem in subsequent pregnancies and with appropriate therapy, these babies have the potential for survival. Sometimes this abnormality can be detected before birth and the baby can be saved.

The most common enzyme deficiency involves the inability of the adrenal to carry out the necessary steps for the production of cortisol. Because of this enzyme block, the adrenal gland is also unable to produce aldosterone which is essential for salt and water balance in the body. As a result, on two of the three pathways in the adrenal (the three roads I talked about before), the principal enzymes are inactive or very much underactive. In other words, main bridges are out on the two roads.

Remember that the body is only interested in cortisol production and it is the production of cortisol that the body regulates very carefully. The other hormones are also regulated but to a much lesser degree.

When the body realizes that there is inadequate cortisol production, it increases ACTH production from the pituitary gland which stimulates the adrenal gland to work harder - the body is attempting to produce more cortisol.

With two of the three bridges out, hormone production is shifted onto the one remaining road open - the road that leads to androgen production.

Consequently, the following syndrome appears at birth. These babies develop adrenal insufficiency very soon after life because they cannot make adequate amounts of cortisol and will die if not promptly and accurately diagnosed. They also cannot produce an adequate amount of aldosterone so they cannot retain sodium. This is termed "salt wasting". Lastly, these babies are producing tremendously increasing amounts of androgen.

Increase androgen production in a baby boy may be difficult to diagnose accurately. However, if the baby is a girl, then the excess androgen production will alter the baby's external genitalia to the point where she will definitely not have the appearance of a normal girl but won't look like a normal boy either. The external genitalia are "ambiguous" and this fact alone will immediately alert the pediatrician that this is a baby with a potentially serious problem.

Going back now to the previous discussion about genes and enzymes, it is important to understand that a person may be born with two normal genes for the enzyme in the adrenal cortex in which case that person will be totally normal since the normal gene is dominant. If a person is born with two abnormal genes for the enzyme, then that person is a pure recessive for that enzyme and it means that the enzyme cannot be produced at all. These are babies born with the disease who are severely affected. Fortunately this situation is fairly rare and occurs only once in about 15,000 deliveries overall.

Much more commonly than having 2 abnormal genes, a person may be born with one normal gene and one defective gene. Therefore, the enzyme is present in deficient amounts and, therefore, the adrenal gland is able to do what it has to but not as well. These "partial adrenal enzyme deficiencies" are fairly common in certain ethnic populations.

Approximately 3% of Jews of eastern European origin are carriers for the most common enzyme deficiency. It is also found with a fairly high frequency in people of Mediterranean origin such as Italians and Greeks. It is, therefore, not rare to see people from these particular groups who have evidence of abnormal hormone production but who are otherwise normal and who lead normal lives. There is a tribe of Eskimos where nearly one third have the defect.

These individuals with the partial enzyme deficiencies usually do not show up until puberty. Women with the partial enzyme deficiency often manifest menstrual irregularities, hirsutism, acne, obesity and infertility. These women resemble people with PCOS and it is often difficult to distinguish between them. In fact, as has been discussed, we are beginning to realize that there is far more interplay between the ovary and the adrenal then we had previously appreciated

It is becoming recognized with increasing frequency that men can have this problem as well. However, it is much more difficult to make the diagnosis. How do you determine that a man is producing too much male hormone? Where the problem is being searched for most diligently is men who are infertile and show evidence of decreased sperm production. This is probably the only area where the partial enzyme deficiency in men has any clinical significance. The only other possible area of concern to me would be those individuals with severe acne, particularly if it persists into adulthood.

Further complicating the problem is the fact that we now know that abnormalities in how the ovary functions affects the way the adrenal produces its hormones. It has been known for years that abnormalities in adrenal function significantly affect the ovary. The opposite is also true.

Therefore, it is not rare to see women with PCOS have increased levels of DHEAS - a hormone produced almost exclusively by the adrenal. This led to confusion as to which problem was causing which. Women with variants of Congenital Adrenal Hyperplasia can exhibit symptoms that are indistinguishable from classic PCOS. Since both problems usually begin at puberty, it can be difficult to determine which is the main problem and which is secondary. (Keep in mind that the most severe forms of Adrenal Hyperplasia manifest themselves at birth. It is only the milder forms that begin later in life.)

If you try to research this, you will come across many terms that have been given to it. One of the more common is "LOCAH" - Late Onset Congenital Adrenal Hyperplasia. It is really an inappropriate term since "congenital" usually means present at birth and therefore cannot be "late onset". Again, it is one of those terms (like PCOS) that may not be correct but everyone knows what is meant by it.

Many times, especially in infertile women, it is necessary to treat both the ovarian and the adrenal abnormalities in order to achieve a pregnancy.

Regardless of what underlying hormone abnormality you may have, the bottom line is this - if you have hirsutism (the presence of hormonally stimulated hair in places where it should not be) you are producing or have produced excess amounts of androgen. It is critically important to understand that there is no such thing as "idiopathic hirsutism." This is a term that you will frequently see in your various readings. It is a term that is frequently applied to women who do not appear to have a hormone problem. The fact is that all women who have hirsutism have a hormone problem. This was proven many years ago by Dr. Mortimer Lipsett and his colleagues at The National Institutes of Health. Dr. Lipsett put his patients through a series of tests that are for research purposes only - they are far too involved to carry out in a regular clinical practice.

What Dr. Lipsett did was to measure the total daily production rate of testosterone - the actual amount of testosterone that the woman produced in 24 hours. This has nothing to do with the serum level of testosterone. What he found was that in women who had hirsutism, there was invariably an increased daily production rate. These women were producing more testosterone than normal. I believe it is improper to label any woman with idiopathic hirsutism. However, it is also true that the tests that we use in clinical practice may not be able to demonstrate the problem but it is there.

One of the principal targets for androgen is the hair follicle - officially called the pilosebaceous unit. In addition to growing a hair, the pilosebaceous unit contains glands that produce an oily substance called sebum. Under the influence of androgen, the sebaceous glands produce this oily substance. If the hair follicle becomes plugged and the oily substance is forced into the surrounding tissues and becomes infected, you develop a pimple. If you develop many of them, we call it acne.

It is important to understand that everyone has hair all over their body. The only exceptions are the palms of your hand and the soles of your feet. Hair follicles in different parts of your body are genetically programmed to produce different types of hair unless subjected to an outside influence.

Basically, there are two types of hair - vellus hair and terminal hair.

Vellus hair is thin and finely textured. It may be light or dark depending upon your own particular coloration.

Terminal hair is thick and course. It is usually dark - at least darker than a given person's usual hair color. The hair on your head is terminal hair. Pubic hair is terminal hair.

It is a misconception that increased androgen makes you grow new hair. What is really occurring is that increased androgen takes a hair follicle that was originally programmed to produce a vellus hair and transforms it into a follicle that produces a terminal hair. No new hair follicle has developed. No new hair has grown. It is a transformation of existing hair.

This transformation occurs normally in boys when they go through puberty because of the significantly increased amounts of testosterone that they begin to produce at that time.

Women, because of their lower androgen levels, only begin to produce terminal hair at puberty in those follicles that are genetically programmed to respond to lower levels of androgen. This would include hair under the arms and pubic hair. If, however, a woman's androgen levels are higher than "normal" hair that should have remained vellus is now transformed into terminal hair.

Hirsutism is defined as the presence of terminal hair on a woman's body in locations where it should not be - hair that is the result of increased androgen levels. As a general rule, the closer to the midline of the body, the more significant the hair is.

The most common locations for such abnormal hair are the chin and the front part of the neck.

Another common location is the lower midline of the abdomen. In women, the top of the pubic hair pattern should be straight across. If there is any growth of the pubic hair up the midline toward the naval, this is abnormal.

Another common site for abnormal hair growth is the midline of the chest over the sternum (the breast bone). Less commonly, there may be terminal hair growth on the upper surfaces of the breasts.

Hair around the nipples, especially if that is the only location, is of little or no clinical significance.

As unsightly as it might be for some women, hair on the upper lip, if that is its only location, again, has no clinical significance.

Hair on the sides of the face in front of the ears is of some clinical significance but, again, some women will have this as their only location and no other. If that be the case, it is of lesser importance.

Other areas in which women may develop rather heavy excess hair growth involves the lower back and buttocks. Usually, hair growth in this area is associated with abnormal hair growth elsewhere.

Some women have excess amounts of body hair and if they are darkly complected, this hair will also be dark. It may be very cosmetically stressful to the woman. However, if there is no evidence of abnormal terminal hair growth, this abundant body hair is simply the way you were genetically programmed and there is nothing that can be done about it. Such excess body hair is termed "hypertrichosis". Unfortunately, there is little you can do to treat this except bleach it.

The following is a description of how endocrine abnormalities lead to the development of hirsutism. It is a multi-step process.

In the majority of instances, there is an abnormality in the way the ovary functions (most commonly PCOS) or the adrenal gland (as in one of the inherited enzyme defects). As has been mentioned, women with PCOS frequently have an associated adrenal abnormality.

The bottom line is an increased production of either testosterone itself or hormones that the body will convert into testosterone. In women who are significantly overweight, conversion of the "pro hormones" will also occur in body fat. This may occur even if there is no underlying ovarian or adrenal abnormality.

As previously discussed, once the increased testosterone is produced, it circulates in your blood stream attached to its specific binding protein. The free or unbound hormone then leaves the blood and enters the cells. Cells that are genetically programmed to respond to androgens will have a receptor specifically for that androgen.

Testosterone then enters the cell and, in the hair follicle, the testosterone is converted to dihydrotestosterone. This process involves adding two hydrogen atoms to the testosterone molecule. Because of the way the testosterone molecule is described biochemically, the enzyme that causes this to occur is called the "5 alpha reductase enzyme". The dihydrotestosterone then stimulates the hair follicle to change from producing a vellus hair to a terminal hair.

Treatment of hirsutism involves an attempt at modifying this change of events at one or more places. All the various therapies that we currently employ are directed at this sequence.

One of the most common ways of doing this is simply to suppress the increased production of testosterone or its pro hormones from either the ovary or the adrenal or both. This can be done directly. In the case of the ovary, oral contraceptives are a common drug that are used with great effectiveness. More potent suppressers of ovarian function, the GnRH analogs (Synarel or Lupron) may also be used.

Adrenal suppression is best carried out with the drug Prednisone. Although some physicians use Dexamethasone, I feel that this is not the best drug. It stays in your body too long and is associated with more side effects than is Prednisone.

Vaniqa is a cream that inhibits the 5 alpha reductase enzyme. Thus lowering the concentration of Dihydrotestosterone in the hair follicle. Used in combination with other therapies, it helps reduce hirsutism. Unfortunately, since most insurance companies refuse to recognize hirsutism as a legitimate medical problem and consider it cosmetic, they will not pay for Vaniqa.

At one time, prior to good drug therapy, ovarian wedge resection was the standard treatment for PCOS. We now understand that it worked simply by physically removing part of the ovary. The less ovarian tissue there is, the less testosterone is produced. We can accomplish the same thing less invasively by laparoscopy. An electric needle is used to burn multiple small holes in the surface of the ovary. This therapy is most effective in women who are trying to become pregnant and for whom the use of Clomid does not result in normal ovulatory cycles.

The problem with any of the surgical procedures is the fact that their effectiveness is relatively short-lived. Since the surgery does nothing to address the underlying endocrine abnormality, within 6 to 9 months the problem has returned full force.

Another approach is to try to modify the way the ovary is functioning. In almost every instance where the ovary is the source of the increased androgen, the woman is either not ovulating or is ovulating very infrequently. If the woman has PCOS and she has been shown to be insulin resistant, treatment with some of the insulin sensitizing drugs such as Glucophage or Actos will often allow normal ovulation to occur. Once normal ovulation begins to occur, the ovarian androgen production is significantly reduced. Problem - there is a Catch 22 in this scenario - namely, that the problem may be so well entrenched that these simpler measures do not work well.

Unfortunately, there is nothing that can be done to change the way the adrenal gland functions. It can only be suppressed.

Birth control pills have an added benefit- more than just simply suppressing the ovary and reducing androgen production. The estrogen in birth control pills increases the concentration of the testosterone binding proteins in the blood stream. The net effect of this is to reduce the free testosterone concentration. This ultimately results in less testosterone that is available to get into the tissues.

SHBG

If you have had the opportunity to review your lab studies or have gotten on the internet (or both) you will frequently see a test called SHBG. It is a test that I always do and it is a test that should be done routinely.

SHBG stands for Sex Hormone Binding Globulin. You may also see it referred to as Testosterone Binding Globulin or Testosterone-Estradiol Binding Globulin. The terms all mean the same. The most common term is SHBG.

It is important to understand that hormones do not circulate in your blood stream by themselves - they are always attached to special proteins, usually of the globulin class. Albumin may also bind some hormones but not to the same degree. Each hormone has its own specific binding protein although some (as in the case of testosterone and estradiol), may share the same protein.

The concentration of these binding proteins is of critical importance if you are going to understand exactly what is going on and if you are going to interpret the tests properly. It is important to understand that the vast majority of each hormone is bound to its own protein (99% or more). Hormone that is bound to the protein is biologically inactive.

The active hormone is that small percent which is unbound or "free". Thus, you will frequently see two tests in your results - the total testosterone and the free testosterone. Another synonym for free testosterone is "bioavailable testosterone".

If there is a large amount of binding globulin circulating in your blood, there are more binding sites for the hormone to attach itself. Therefore, the free or unbound portion will decrease.

Conversely, if there is a lower concentration of binding protein, there are not enough binding sites for the hormone to attach to and, therefore, the percentage of the hormone that is free or unbound will increase.

Simply measuring the total testosterone is not enough. Unless you know the concentration of the binding protein, you cannot accurately interpret the testosterone concentration.

This same principle applies to other hormones as well, most commonly thyroid hormone.

Many things will influence the concentration of the binding proteins in your blood stream. In general, estrogen increases the concentration of the binding proteins and testosterone lowers the concentration. This compounds the problem. As a result, a woman may have a normal total testosterone level but if her SHBG level is low, her free testosterone level will be elevated. Failure to recognize this will often lead people to conclude that there is no hormone problem when in fact, there is.

However, in discussing androgen problems, one other hormone that must be mentioned is of critical importance and that is insulin. Studies have now clearly shown that insulin reduces the concentration of SHBG. This is highly significant for several reasons. First, if the SHBG concentration is low, the free testosterone level will be increased even though the total testosterone may be normal. Given this fact, I hope you can now appreciate that simply measuring the total testosterone without measuring the SHBG gives you an incomplete assessment of a woman's true hormonal status and may lead you to conclude incorrectly that there may not be a hormone problem.

Of equal importance is the fact that a low SHBG level implies an elevated serum insulin level. It now seems fairly certain that a low SHBG concentration in your blood stream is the biological equivalent of hyperinsulinemia and insulin resistance. We have known for some time that a low SHBG level is a risk factor for cardiovascular disease. We never knew why - now we do.

It is a relatively simple calculation, using the total serum testosterone and the SHBG concentrations to generate a number that we call the Free Androgen Index or FAI. A normal woman does not have a FAI greater than 5. If the calculation shows that her FAI is in fact greater than 5, this indicates that she has elevated levels of circulating androgen even though the actual concentration may be "normal". This is why I have seen a number of women over the years who were told that they did not have a hormone problem because their total testosterone level was "normal". As I have discussed elsewhere, this, in part, may be due to the fact that the normal range given by the lab is incorrect. It may also very well be due to the fact that the SHBG concentration was never measured and, therefore, a true picture of that woman's hormonal status was never obtained.

GENES, CHROMOSOMES AND HEREDITY

Each of us is who we are because of heredity. Heredity is nothing more than the passage from one generation to the next of those physical features (and otherwise) possessed by our parents. Their parents passed along certain features to them and so on back through the generations.

Every piece of information that determines who we are is carried in our genetic code. Each unit of the genetic code is called a gene and genes are found on chromosomes.

Chromosomes are strands of DNA found within the nucleus of the cell and are made up of thousands and thousands of individual chemicals called nucleic acids.

There are four different nucleic acids and each group of three nucleic acids on the DNA codes a specific amino acid. Remember that proteins are nothing more than chains of amino acids strung together like beads. You can now appreciate that the chromosomes are nothing more than master blueprints for proteins. Proteins are our body's building blocks and every different protein in our body carries out a different function. Nothing happens in the body that is not under the regulation of at least one and often more than one protein.

A human being contains 46 chromosomes. However, they are not 46 different chromosomes; they are arranged in 23 pairs of chromosomes. Each sperm and each egg contains 23 chromosomes and when sperm and egg unite to initiate the process of fetal growth, the resulting baby that is formed has a total of 46 chromosomes.

These chromosomes are grouped into 22 pairs of what we call the body chromosomes or autosomes. The remaining pair is called the sex chromosomes. If you are a male, you have an X and a Y sex chromosome; if you are a female you have two X chromosomes.

When a cell divides, the chromosomes duplicate themselves so that each two cells that are formed contain the identical chromosomes as did the parent cell that formed them. However, the process of duplication does not always proceed correctly and mistakes may be made. These mistakes involve incorrect duplication of the nucleic acids which means that the genetic code for any one sequence is disrupted and that means that the protein formed will be defective in some way.

These defects in the duplication process are called mutations.

In an attempt to minimize the damage created by a mutation, mother nature has given us duplicate sets of chromosomes for each function - for each protein. Therefore, if one doesn't work right, at least there is another there that will do the job correctly.

Chromosomal abnormalities and genetic mutations are a lot more common than people realize. However, in the vast majority of instances, either they are of no consequence because the other chromosome is able to take over the job or the defect is so devastating that it never permits embryo development to take place and the woman has a miscarriage.

There are, however, various genetic mutations that fall somewhere in between and these often result in diseases that we can now recognize and often treat.

In many instances, a person will have two genes for the same characteristic and neither gene is harmful or dangerous - just different. Such a characteristic would be eye color. If there are two genes for the same characteristic and one predominates or takes over, that characteristic is called "dominant" and the other characteristic which is suppressed is called "recessive".

In the case of eye color, brown is dominant over blue. Therefore, if a person has two brown-eyed genes, they would be obviously brown eyed. If a person had two blue eyed genes, their eyes would be blue. However, if a person has one gene for brown eyes and one gene for blue eyes, their eyes will be brown.

To further confuse you, many genetic characteristics are not "all or none", there can be what is termed incomplete dominance. In the case of eye color, your eyes might be hazel or green.

There is another important feature of the way your body functions that you must understand. All chemical steps within your body proceed in a very tightly controlled fashion and each step in each chemical process is controlled by what is called an "enzyme". Enzymes are mother nature's catalysts and determine that certain chemical reactions always take place in a certain manner and only in that manner.

Enzymes are proteins and you can now begin to appreciate that if there is a genetic mutation, a given protein was not formed properly. If that protein is an enzyme, then a given chemical reaction within the body may not proceed the way it should.

As with almost anything else in medicine, there is always going to be an exception. As I have already discussed, there is no such thing as idiopathic hirsutism - studies done many years ago clearly showed that if a woman has androgen stimulated hair on her body in areas that are not normal, such as the chin, front part of the neck, between the breasts, etc., then that woman is producing excess amounts of androgen. When most people think of excess androgen production, they think of either the ovary or the adrenal gland or the body fat as the source of that excess androgen production and in fact, for the vast majority of women, this is the source. There is, however, a small group of women where the actual problem is in the hair follicle itself. This problem is hereditary and is genetically determined. Hence, I have included it in this section.

As I have mentioned, the hair follicle itself is very metabolically active. Dihydrotestosterone is the hormone that stimulates the hair follicle and causes it to produce course dark hair. Dihydrotestosterone is produced in the hair follicle by the conversion of testosterone itself and the enzyme which controls this conversion is called the 5 alpha reductase enzyme.

The vast majority of women with hirsutism have increased production of testosterone. Therefore, there is an excess amount of testosterone available to the hair follicle which drives the reaction forward and results in the increased production of dihydrotestosterone.

However, there are a small group of women whose total daily testosterone production is normal - their problem is an excess level of activity of the 5 alpha reductase enzyme leading to an increased conversion of testosterone to dihydrotestosterone. In cases such as this, although therapies directed at reducing total daily testosterone production play a role in therapy, blocking the 5 alpha reductase enzyme also plays a significant role. This will be discussed in the section concerning treatment.

©2003 Michael D. Birnbaum, MD, PC - All rights reserved

All materials on this site are property of Michael D. Birnbaum, MD, PC

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That's for posting that, long but an interesting and worthwhile read for me as I've been on spironolactone for nearly a month.

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to the post above: you can use spironolactone. look it up. it is prescription, but it is ONLY for WOMEN who have unbalanced hormones. if you have neck/jawline acne, hirsutism, and oily hair/skin...these are signs of hormonal acne. spironolactone is great at remedying this imbalance.

it takes up to 2 months to work, but it does work. the best thing is that there are no harmful side effects (unless pregnant)..the worst is that you have to pee a lot b/c it is a diuretic.

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