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December 26, 2005


Question from Ontario, Canada:

I have type 1 diabetes. I am on the Cozmo pump and use Humalog. I also have PCOS and take cyproterone acetate, or Diane 35, as it is known in Canada. What can you tell me about this drug? I am told it is dangerous and some countries have different rules governing it use. However, I know my hormone levels, like my DHEA-sulfate, are back in range post Diane 35, and they never were on Alesse, or orthotrycyline. (I do not know what these are called in the U.S.) So what can I do? What if they recall Diane 35? How important is it for my DHEA-sufate, free testosterone, etc. to be in range? Also, my health care team is not too on top of my PCOS and I have had an elevated cortisol level in the past (assessed via blood draw). So, I was wondering what tests should I be asking my family doctor and endocrinologist to do for my PCOS? I was told the elevated cortisol level was from being on oral contraceptives. Another endocrinologist I saw, where I attend university, said the best way to figure out what is going on with the cortisol issue is a 24 hour urine collection. However, I was living in residence at the time, so I passed on that opportunity. What is the best test to determine if my cortisol levels are elevated?


Let’s discuss the cyproterone first.

The male hormones, such as testosterone and androstendione and DHEA-S, are called “androgens.” Cyproterone is an “androgen blocker.” This drug is not available in the U.S. In a simplistic manner, hormones work by interacting with individual cells of various organs. But, the cells don’t just have an “open door policy” i.e., the hormone chemicals don’t just pour into the cells. The cells must be “unlocked” to let the hormones come in. (Maybe think of the hormone as a “key” and in order for this chemical to get into the cell, it must interact with a “lock.” We call the lock a “receptor.”)

Cyproterone interferes with or “blocks” the receptor from interacting with the androgens and, therefore, the effects of the androgens upon those cells will be diminished. If that cell is, for instance, one that produces facial hair, then we’d hope the cyproterone would lead to less facial hair.

But, I would then expect the measured androgens in the blood to be INCREASED (not decreased) with cyproterone therapy and not “in range” as you had assumed: if the blood hormone levels are not being taken in by the cells and used up, then the levels will accumulate in the blood.

One of the potential risks of cyproterone is its affect upon the developing fetus in a pregnant woman. If the cyproterone interferes with the effect of male hormones, you can see how this might lead to malformations of the genitalia, especially in a male fetus.

The elevated cortisol is another story, and one that is probably not worrisome. Cortisol is a hormone of “stress.” When we are sick, injured, anxious, scared, etc., we make more cortisol from the adrenal glands which sit atop the kidneys. We also tend to make for cortisol in the morning, around breakfast time. So, a high cortisol level may reflect time of day or it may reflect “stress” (anxiety associated with being stuck by a needle), or concurrent illness, or strenuous activity. Or, it could reflect someone whose adrenal glands are inappropriately making cortisol.

To try to clarify matters, then, one would want to collect a complete 24 hours’ worth of urine to measure cortisol over the full day with its ups/downs, etc. For example, you likely wouldn’t make much cortisol while sleeping and inactive. If the 24 hour excretion is normal, then the less likelihood of a serious process.

There are a number of ways that PCOS can be assessed: commonly one will measure the unbound (or “free”) testosterone and perhaps the measurement of the pituitary hormones called LH and FSH. But, being on the androgen blocker may make those measurements quite hard to interpret.