Androgens and Ovulation

Androgen is the generic term given to any hormone that directly or indirectly produces male characteristics. The principal androgen in the body is testosterone but there are a number of other hormones which the body can easily convert into testosterone. The principal hormones that fit this category are androstenedione and DHEA (De-Hydro-Epi-Androsterone). Androstenedione is made in both the ovary and the adrenal and each contributes about 50%, under normal circumstances.

DHEA is produced almost exclusively in the adrenal. The body quickly adds a sulfate molecule to the DHEA and the principal form of this hormone that is found in the bloodstream is DHEAS.

There are three sources of androgen in women - the ovary, the adrenal gland, and body fat. In women who are significantly overweight, body fat can play a significant role. It is probably of little significance in women who are of normal body weight.

Androgens play a critical role in the ovulatory process. In normally ovulating women, androstenedione is produced in the ovarian cells that surround the developing follicle. The androstenedione then moves from these cells into the cells of the follicle itself where it is converted into estradiol.

In women with an ovulatory abnormality, particularly women with Poly-Cystic Ovary Syndrome (PCOS), the ovarian cells around the follicle often produce excess amounts of androstenedione. This becomes all the more important when you stop to realize that if the follicle never develops properly, the androstenedione cannot be converted into estradiol. Instead, the body will convert that androstenedione into testosterone.

The woman then becomes locked into a vicious cycle. If she is not ovulating properly or not ovulating at all, she starts to produce excess androgen. Excess androgen itself will block the ovulatory process. It then becomes a self perpetuating problem.

When we assess ovulation, we are looking at all of the hormones produced, including the various androgens. Some women who appear to be ovulating normally will produce excess androgen during the menstrual cycle, indicating that there is in fact an ovulatory abnormality.

We also assess androgen production in women who are undergoing ovulation induction programs with either Clomiphene or one of the injectable gonadotropins. Although most women who receive these medications do not show any significant elevation of their androgens during the menstrual cycle, a significant percentage do. The question is whether or not this increased androgen production in response to the Clomiphene or the gonadotropin therapy has an adverse effect on ovulation and whether or not it may interfere with that woman's ability to become pregnant.

It is already well established that women who do not ovulate or do not ovulate normally, who are candidates for Clomiphene and who also show evidence of increased androgen production, must have that androgen production suppressed in order for the Clomiphene to work. This is particularly true when the evidence indicates that the principal source of the excess androgen is the adrenal gland.

Although several studies have been done looking at elevated androgen production during stimulated menstrual cycles, there is not, as yet, any definitive answer as to whether this is detrimental or not. Nonetheless, we take the position that these elevated levels are not normal and, therefore, may be interfering with the establishment of a pregnancy in ways that we cannot determine. Since most women do not show an elevation in their androgens during the menstrual cycle, spontaneous or stimulated, it certainly raises questions and concern - at least in those instances when the woman is showing an increase.

We therefore take the position that if a woman is showing a significant elevation in her androgens, particularly during a stimulated cycle, since we cannot prove whether it is harmful or not, it seems prudent to try to reduce those androgen levels to whatever degree can be reasonably accomplished. It is sometimes exceedingly difficult to determine whether it is the ovary, the adrenal, or both that is the source of the excess androgen. Obviously, we cannot suppress the ovary - that would block ovulation and prevent a pregnancy. We therefore attempt to suppress the adrenal gland in the hopes that lowering overall androgen production in the body may improve the ovulatory process.

The drug traditionally used to suppress adrenal production is Prednisone. Many people, when they hear the word Prednisone, become very concerned. Most people's familiarity with this drug involves relatives or friends who are taking it in high doses for the treatment of severe asthma, various autoimmune diseases, or a variety of other medical problems. It is critically important that you understand that the dose of Prednisone that is used to suppress adrenal androgen production is very small compared to the amounts used to treat other illnesses. Therefore, the side effects that are associated with very high doses of Prednisone do not occur at the doses we employ. In fact, it is quite rare for anyone to have any side effects whatsoever.

Prednisone is taken as a 5 mg. tablet each night at bedtime. The way the adrenal gland functions, it produces most of its hormones at night while you sleep. Therefore, we can achieve adequate adrenal suppression by taking the Prednisone at bedtime.

As we have just mentioned, at the doses we use, side effects are minimal to none. Prednisone does not interact with any other medication and you can take aspirin, any common over-the counter drugs, any other prescription drug, and you may also drink alcoholic beverages (although you should be careful if you are trying to become pregnant).

There are only two precautions that must be taken if you are taking Prednisone. First, you must not stop the drug abruptly. It should be tapered over several weeks and if we make the decision to stop the drug, please let us instruct you as to how to properly do it.

If you should become pregnant while taking the Prednisone, do not stop it. It does not harm the baby.

The other precaution that must be taken is that any physician who is treating you for any other problem must know that you are taking this drug. If that physician has any questions, please have them call us.

In addition to suppressing adrenal androgen production, Prednisone is also suppressing adrenal cortisol production. Cortisol is one of your body's main "stress" hormones. In a serious stress situation such as surgery or a serious illness, your body will produce significant amounts of cortisol. We are deliberately interfering with that. Therefore, if you should need surgery, make sure that the surgeon knows you are taking this drug.

If you should develop a serious illness, we will have to increase the dose of Prednisone temporarily to mimic what your body would have otherwise done. You do not have to increase the Prednisone for a mild respiratory infection but if you run a fever that is over 101, you must call us.

You do not have to increase your Prednisone for a simple cavity. However, if you need more extensive dental work, particularly if there is an infection present, please contact us as we may have to temporarily alter the dose.