Testosterone Clinical Trial – Video

Can Testosterone Improve Ovarian Function in Women?

Dr. David H. Barad discusses a CHR clinical trial that treats female infertility with testosterone.

Video Transcript

Title: Testosterone Clinical Trial Instructions

Speaker: Dr. David Barad

Patients’ Guide to CHR’s Testosterone Clinical Trial

Background of testosterone clinical trial: Roles of DHEA and androgens on ovarian function

At CHR, we’ve been very interested in looking at ways of trying to allow ovaries to function better than they do on their own. So there’s a whole class of women who have been told that their ovaries are not functioning well, that some of them are not functional because of age — they’re over age 40 and it’s expected that ovaries decrease in function — but we’ve even seen some younger women who have been told that their ovaries are no longer going to be able to produce sufficient eggs for them to be able to achieve pregnancy, and they’ve already had recommendations to use donor eggs.

A lot of these patients have been coming to us over the last few years. One of the ways that we’ve been dealing with them over the last 5 or 6 years is with DHEA. DHEA is an androgen: it’s a weak male hormone, and it appears to have some positive effects on how the ovaries work. In order to understand that, you have to understand a little bit about ovarian physiology.

I’m not going to bore you with the whole physiological explanation, but basically, functionally, as far as the ovary works, all the eggs in the ovary have been there all of a woman’s life. You can think of most of them being warehouses, just sitting there waiting, and then slowly, little by little, just on a regular basis they start moving from that warehouse state into a functional state. They’re kind of like the eggs that are on deck. We’ve just come through the Olympics, so these are the ones that are in high school, these are the ones that are on deck training to compete, and finally you have the ones that are actually in the menstrual cycle that are going to ovulate.

It turns out those ones that are on deck you can think of as being in some sort of a box or a training state; they are very sensitive to some hormones, and one of the hormones that they are increasingly sensitive to as they progress through that state is an androgen type of hormone like DHEA. DHEA is a very weak androgen, but it seems to have positive effects in many people, and for many of our patients we see a good response and we see increases in ootocyte numbers and ootocyte quality as they take the DHEA.

Well, we became interested over the last year or two over why some people don’t respond to DHEA. What’s different about them? And so we were looking at the hormones that are circulating in those women — those who respond and those who do not — and we’re trying to make some comparisons. And it turns out that the women who seem to have the best response, who got the best eggs, the best-quality embryos, and were most likely to get pregnant, were women who increased their testosterone after they took DHEA.

Now, to understand that, you have to realize that hormones come on an assembly line, and DHEA is one of the raw materials that can become testosterone. Testosterone, which is the strongest male hormone that most of us know of, is the precursor to estrogen. So every woman who goes through life and is womanly and has estrogen, has estrogen because she also has testosterone. So that if you have normal ovarian function you have to be able to make some testosterone, or hormones like testosterone, in order to have estrogen at all. So it is not surprising that women who started out with poor ovarian function and very low testosterone took DHEA and their testosterone came up, that those women are the ones who had the best response to the DHEA.

We became interested in trying to answer a question for those women whose testosterone doesn’t come up when they take DHEA: if we give them testosterone, is that going to improve their situation? And that’s what this new study is addressing, the question of, "Can we use testosterone to improve ovarian function in women that weren’t responsive to the DHEA?”

What will be measured in the testosterone clinical trial?

The women who are qualified to be in this trial are women who have evidence of poor ovarian function because they have high FSH and low AMH. They need to have already taken DHEA and have not had a good response in an IVF cycle. So they’ve taken the DHEA, their testosterone didn’t come up, and when they went through an IVF cycle they had a poor response, not very many eggs, or very poor-quality embryos. What we’re looking to do is in a subsequent IVF cycle, after they’re taken the study medications, to then see if the hormonal perameters improve, if the number of the eggs improve, if the quality of the eggs improve, and, of course, if we have more pregnancies.

What is the overall goal of the testosterone study?

If we knew that testosterone treatment was a good treatment, we wouldn’t have to do a study, and we would just be prescribing it to people. At this point, it’s in question, and so the goals of any study are to see, Is your treatment effective? Is it practical to use? And is it safe? Those will be the goals of this study.

How can a patient participate in the testosterone study?

People who qualify will be asked to participate in a randomized controlled trial, which means that some will get testosterone and others will just get the placebo. We won’t know who’s getting what, the patients won’t know who’s getting what, and that’s because it’s a blinded, randomized trial. Our study coordinator, our statistician, will know because she’s doing the randomizations. So there is somebody looking, and if it becomes necessary to know to find out for safety reasons, but in general we will not know.

What form does the testosterone come in?

We’re giving this testosterone as a cream that is absorbed through your skin, and so it’s a cream that comes in a pump. Each pump will deliver a small amount of the cream. It’s a measured amount. Each measured amount, if it’s the testosterone, will have half a milligram of testosterone in it. If it’s placebo, it won’t have any, but it will look the same and it will be in similar packaging. And the woman will just rub that in to the skin of their left wrist. We’re asking everybody to use their left wrist so we can keep track of any local skin effects from the cream. They’ll do that on a once-daily basis, and we will see what their response is.

How long will testosterone or placebo cream be used?

They need to do that for six weeks before they start the IVF cycle, because, we believe, it takes about a month, a month and a half, for the effects on the early follicles to be present so they can have benefit when you come into the ovulation induction cycle.

Is testosterone safe to use?

Testosterone has been on the market for years for treating men. The male transferrable testosterones are all much stronger than what we’re planning on using for women. We’ve done some preliminary trials — testing, using this particular cream — and the women who use this cream will be raising their testosterone to normal levels that are seen in reproductive-age women, not to levels that would be seen in a man. So you’re not going to grow a beard, or lose your hair, or change your voice. You’re going to have the same levels as an average reproductive-age woman. We’ve tested this in a number of women, and it seems to be true. We’ll be doing safety monitoring of them as they go through the trial to see what they’re response is. If any level comes up above a certain point, the lab will notify us and then we’ll respond to that, but so far, in the preliminary trials, nobody has even come close to the safety margin.

Why can’t CHR just start treating women with testosterone?

It’s very important to answer these questions and not simply say, "Well, gee, I want the real stuff," because we don’t know if it’s a useful thing. We can answer this question in a randomized trial with the help of not too many women participating. If you just start giving people the treatment, it may take years to answer the question before you collect enough data, and a randomized trial is the most powerful way of seeing this difference. If we are able to show a difference, then within a short while we’ll be able to offer this to people on a regular basis. We’re all in this together, we all have the goal of trying to help people achieve their goals of pregnancy, and I’m very grateful to our patients who help us to answer these questions, and that way we’ll all be in a better position.

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Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned reproductive endocrinologist, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.