This Is the Sex Education you Missed

Brett Berhoff launches his latest interview. I had the pleasure of meeting one of the great minds of the medical world, Dr. Virginia M. Miller of Mayo Clinic. Her research into sex hormones and sex differences is groundbreaking in the treatment of individuals based on how a disease affects them as either male or female.

Dr. Miller currently serves as the principal investigator for the Specialized Center of Research on Sex Differences and has written more than 250 original publications.

We discussed her research and the implications it could have on the medical treatment of men and women:

Before we get into anything else, I'm curious about how you even picked this field or interest. What piqued it for you to laser focus on this world of sex differences?

I had a fellow who was interested in looking at some of the sex differences in the pediatric population, and it just sort of blossomed from there. It was a progression. I became the advocate in the medical community showing the need to look at sex differences. This was in the mid-90s, and there wasn't really a lot of detailed research on it then.

From the perspective of a non-medical professional, studying sex differences seems logical, especially given that medicine is often tied to ethnic backgrounds, lineage, and so forth. Why do you think it was overlooked?

Well, I think it depends on the discipline. For example, in the field of neurology, the idea of sex differences in the brain has been entrenched in their thinking for a long time.

When you're trying to identify a difference between two groups, the more variable a group is, the harder it is to find a difference; you want to reduce that variability as much as possible. The thinking became, “We shouldn't study female animals because they've got this cyclicity thing going on, which adds to the variables.”

A significant idea that influenced taking women out of clinical trials was the idea that the studies had been conducted with Thalidomide, which was believed to create birth defects. We don't want to enroll any women in studies because what we might be intervening with could harm a fetus or create birth defects in the future. With all of these factors considered, the idea of studying pregnant women or making sure women weren't pregnant when they were included in clinical studies was just abandoned, and so women were forgotten about in the study altogether.

Of course, we have since seen studies that have evaluated all the variability and studies that use female animals. And the conclusion of those analyses is that the data is not really as big as it was once thought to be. There's actually more variability in male animals. The idea that the female animals are more variable is just now debunked.

Could you go into more detail about these studies? Is the goal to look at these sex-specific differences for how it will benefit all ages all the way down to in utero?

Actually, there are investigations from conception on, in terms of how sex differences might play out. For example, if a male baby might be influenced differently by the mother's physiology, you know her risk factors, her behaviors may impact that male baby differently than a female baby. And some of those data go back to World War 2 where women from the Netherlands who were exposed to starvation conditions during various stages of their pregnancy. Their sons ended up with greater cardiovascular risks than their sisters or other girl babies born during that same time. So, the idea that the in-utero environment can have a sex-specific effect on a baby that's developing and that baby's risk throughout the lifespan is a really active area of research right now. And likewise, the environmental factors that children are exposed to can affect their genes. It's called epigenetic regulation of how the genes are influenced by the environment and how those changes influence propensity for disease across the lifespan.

I would love to hear you talk about the differences between sex and gender and the definition of a sex hormone? What's estrogen? What's testosterone? The general public hears these words, but their understanding of them is potentially limited.

There is a lot of confusion about these words. Sex is biological and deals with the kinds of sex chromosomes you have. Female sex chromosomes are two X's. And the male chromosomes are an X and a Y. Now, this is genetic material that is in every cell and dictates whether it is a male cell or a female. There can be some abnormalities with those chromosomes, but that’s a conversation for another time.

So, you have all the cells of the body with these X and Y chromosomes. The cells have a sex even without talking about hormones or anything else. Now, because you have these chromosomes, they dictate the development of the sexual organs. In the males, that would be the development of the testes, and in a female, that would be the development of the ovaries and these organs, the testes and the ovaries, produce hormones called sex hormones. Although you can find sex hormones in both males and females, the balance is that in males, testosterone is the main sex hormone and in females, estrogen is the major sex hormone. Although you can measure testosterone in women and you can measure estrogen in men, they have specific biological effects.

Gender, on the other hand, is a set of sociocultural constraints in which an individual must operate. There are certain expectations if you are a biological male. There used to be expectations, for example, that men would be into physical labor and be the breadwinners of their families, and the women would be caring for the children and have more sedentary type jobs, such as being a secretary. Now, these gender expectations are beginning to not exist as one or the other. There's really a continuum, and you would find that an individual throughout his or her life or even throughout his or her day may exhibit more what was typically characterized as male characteristics (masculine) of being opinionated or aggressive or authoritative and female characteristics (feminine) to be more submissive or loving or caring or social. But now that spectrum has broadened, and you probably can identify yourself during the day, your day, when you find yourself exhibiting more or less of one of those characteristics that exist on a gender spectrum.

Your research focuses specifically on the study of sex differences and the implementation into medical research for the outcomes of specific medical conditions in both sexes?

Oh, absolutely and that's why there's an initiative to talk about sex and gender-specific medicine of which both men's health and women's health is part. Because again, remember we have sex chromosomes, and we have gonads, which produce different hormones. So there really are sex-specific conditions. For men, prostate cancer is a sex-specific condition. Erectile dysfunction is a sex specific condition. For women, pregnancy is a sex-specific condition. So, within the individual and within the sexes, there are conditions that need to be studied and understood to improve the health related to those conditions. Remember, there are some diseases which both men and women get.

What can the general public do to help the medical community push this initiative forward?

Well, they can start asking their doctor what's the evidence that this treatment is best for them. I think women need to ask if the treatment was tested in women. They may say I don't know, or yes or no. Start by asking the questions.

Physicians themselves need to be educated on these kinds of issues as well. You don't take it for granted that everybody here at Mayo Clinic or anywhere else is tuned in to thinking about sex differences in what they do because it's just not there.

There has been such a culture of talking about patients in general and generalizing medicine to treat the biggest group driven by some sort of population science rather than the science of treating the individual.

What do you think people will say about studying sex differences in 20 years?

We will reach a point where people are going to say what!?, this was an issue? Because it'll just be this is how we think. This is how we operate.

Looking forward to hearing your comments below!

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