NARRATION

It's said testosterone is the hormone that makes men... well, men. It sculpts the male body, increasing muscle mass and bone strength, and moulds the male mind, fuelling libido, risk-taking and the pursuit of status.

Professor Robert McLachlan
But it's selling the hormone well short to say that's all it does, 'cause it has effects throughout the body.

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Its impact begins in utero.

Professor Andrew Whitehouse
Those nine months that we're in the womb may actually affect the rest of our lives.

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And it affects us all.

Professor Susan Davis
Women have more testosterone circulating in their blood at any time than they have oestrogen, so testosterone's a really important hormone for women.

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But while having too much is often perceived as a social poison, inciting acts of aggression, having not enough is... well, not good enough.

Dr Graham Phillips
Testosterone is just a molecule, and yet it has an enormous impact on us. Just how does it affect our abilities, behaviour and health? Well, we're about to find out...

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..starting in a hedge maze in southern Victoria. This is Adjunct Professor Richard Wassersug, an expert on the effects of androgen deprivation therapy - ADT. It's a drug treatment for prostate cancer, and stops the production of testosterone to prevent the growth of the cancer.

Adjunct Professor Richard Wassersug
High levels of testosterone activate the prostate gland, and if there's prostate cancer cells they can inspire them and stimulate them to grow.

Dr Graham Phillips
Now, Richard and I are going to enter this maze at opposite ends, and our task is to get to the garden at the centre using just this aerial map as a guide.

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But research suggests Richard may be at a disadvantage because of his own lack of testosterone. Testosterone is a hormone - a chemical messenger that travels the bloodstream to communicate with the cells throughout the body. In men, 95% is produced in the testes. In women, most testosterone is produced in the ovaries and adrenal glands, but it's only 1/10th of the level that it is in men. So, what's testosterone got to do with finding your way through here? Well, my testosterone is within the normal adult range - roughly 10-30 nanomoles per litre. But Richard, like more than 20,000 Australians, has had his testosterone production completely turned off because of his treatment for prostate cancer.

Adjunct Professor Richard Wassersug
Personally, I was intrigued by how different my brain worked when I went off of testosterone. So, indeed, I experienced it myself, and it inspired me to look into it deeper as a scientist.

Dr Graham Phillips
Now, there is some evidence that losing testosterone because of ADT does affect a man's ability in navigational tasks like this.

Adjunct Professor Richard Wassersug
This is confusing. It's actually problems like working through a maze or finding your car in a parking lot that are the actual cognitive challenges that these men have. I certainly, having been off of testosterone, I find these challenges to be very real. In fact, actually, this is sort of known already because women typically use a slightly different navigational strategy than men. Women pay attention to landmarks, and it appears to be related to testosterone.

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On the other hand, men tend to navigate using distances and direction. It's thought this plays into testosterone's visuospatial strengths. In general, men perform better than women at mentally rotating three-dimensional objects or manipulating a map in their mind.

Adjunct Professor Richard Wassersug
But that doesn't mean they're necessarily better at all areas, and, for various ways of getting around, sometimes knowing where things are and exactly where they are is an advantage.

Dr Graham Phillips
I'm not sure that either strategy's any good in here.

Adjunct Professor Richard Wassersug
Since I knew that women could use landmarks, I tried to develop a landmark approach to navigation.

Adjunct Professor Richard Wassersug
I think, as an aside, we could be helping patients by letting them know this - because they're afraid they're going to get lost when they don't have testosterone to blindly lead them in the right direction.

Dr Graham Phillips
Hey, Richard, how are you going?

Adjunct Professor Richard Wassersug
Hanging in there! I think I'm gonna be able to find my way out.

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We'll come back to Richard later. Testosterone has also been found to affect the abilities of women as they age.

Professor Susan Davis
When a woman hits menopause, oestrogen is going along and it goes plonk - it falls precipitously. In complete contrast, the fall we see in testosterone starts in women in their mid-20s. So, by the time a woman is in her 40s, her testosterone level is about half as what it would have been in her 20s.

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In a recent study, Professor Susan Davis tested the mental rotation ability and verbal fluency of post-menopausal women after 26 weeks of testosterone therapy.

Professor Susan Davis
She'll rotate them and then decide whether they're a mirror image of the letter.

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The study found that after taking the course of testosterone, those areas of the brain activated by the tasks lit up less than beforehand.

Professor Susan Davis
What this is really telling us is that testosterone is enabling these women to perform a mental task, but using less brainpower to do it.

Dr Graham Phillips
So, their brain was finding it easier.

Professor Susan Davis
Their brain was finding it easier.

Professor Susan Davis
What we hypothesise is that when women's testosterone levels fall, they still function normally, but there's functioning below par for them. And that's why women often say, 'My memory's gone, I'm not as sharp as I used to be,' but they're still performing their job.

NARRATION
Testosterone's role in shaping our abilities begins in the womb. In the first weeks of life, the human foetus has neither testes nor ovaries - it simply has gonads, which, if left alone, will develop into ovaries. So, the Y chromosome in males triggers the development of testes, and, with them, testosterone to masculinise both the male's brain and body. Increasingly, researchers are studying the effects of this early flood of testosterone.

Professor Andrew Whitehouse
There is so much evidence now that adult health and disease is driven by what happens in utero. And we're thinking more and more that testosterone has a big influence in how our brain develops.

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Professor Whitehouse's research is focused on child development, including language delay.

Professor Andrew Whitehouse
We've done a number of studies. The first one, what we did is we looked at testosterone collected from umbilical cord blood. Now, it's a really cool technique where we actually take the cord blood from birth and then analyse that for how high the levels of testosterone are. What we found is that those kids who have the highest levels of testosterone, they're actually at an increased risk for language delay early in life.

Dr Graham Phillips
Does that language delay correct itself or is that a long-term effect?

Professor Andrew Whitehouse
What we do know is that language is quite unstable during the early years - you can be quite delayed and catch up very quickly, or you can be advanced and then slow down quite a lot.

Professor Andrew Whitehouse
What we've found is that this testosterone is linked to quite severe language delay that actually does last into early adulthood.

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In a unique study, Andrew and his team explored testosterone's role in shaping the architecture of the brain and looked for a potential link with language delay.

Professor Andrew Whitehouse
What we then wanted to find out is... well, what's the mechanism? Is it do with the notion that language centres are on one side of the brain or both?

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About 90% of people have their language centres specialised to the left side of their brain.

Professor Andrew Whitehouse
Why? We think testosterone may affect a part of the brain called the 'corpus callosum', which is the part of the brain that transfers messages from one hemisphere to the other.

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To test the theory, they re-examine the umbilical cord blood or all the children who had recorded high levels of testosterone 20 years ago, this time using a more precise method of mass spectrometry. The brains of those children who are now adults were then tested using this.

Simone Fernandez
So, we'll start off by putting on the cap on your head.

Dr Graham Phillips
Right.

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A functional transcranial Doppler ultrasound.

Simone Fernandez
We find that we're looking out for a whooshing sound.

Dr Graham Phillips
And that's the actual blood whooshing that you're hearing?

Simone Fernandez
Exactly.

Dr Graham Phillips
This is an ingenious device. There are two ultrasound generators - here and here - and they're measuring the speed of the blood flow through the main arteries that feed my brain.

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When a part of the brain is activated, more blood flows to that region, so a language test reveals which side of the brain a person's language centre is on.

Simone Fernandez
This is a word generation task. You'll see a letter appear on the screen. I want you to think of as many words as you can that begin with that letter. Then, you'll hear a tone, and I want you to say the words.

Dr Graham Phillips
OK.

Simone Fernandez
OK?

Dr Graham Phillips
Android, alternative, ape.

Professor Andrew Whitehouse
What we found is that those children or those adults who are exposed to high levels of testosterone in utero, they were far more likely to have a pronounced pattern of lateralisation. That means that the lateralisation was far more on the left side than anywhere else, and we actually think that that relates to testosterone compromising this flow of information from one side of the brain to the other, in utero.

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Testosterone also has the potential to affect our behaviour...

Dr Graham Phillips
How are you?

Adjunct Professor Richard Wassersug
Grand.

Dr Graham Phillips
You made it!

Adjunct Professor Richard Wassersug
Yes!

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..as Richard found when he became testosterone-deprived.

Adjunct Professor Richard Wassersug
I feel fairly lucky. I mean, a lot of patients get depressed on these drugs and, of course, they get depressed perhaps because there's problems with memory that can happen in some of the patients. I've certainly found that it's affected my interaction with women.

Dr Graham Phillips
Really?

Adjunct Professor Richard Wassersug
Well, testosterone drives male libido. And I've found I was less drawn by an attractive woman's body as it went by, but I also found that faces were very much more interesting and that I could appreciate what people's expressions were, and women are far more attentive to facial expressions.

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Now, Richard's hardly alone. Studies tracking eye movement have shown that while men are fast to fixate on breasts, the hip-to-waist ratio and the faces of women, women are likely to focus more quickly on faces. Women also have more empathy - another quality related to testosterone levels.

Associate Professor Tom Denson
In general, men with higher levels of testosterone are lower in empathy, they're less attendant fathers and also, if you experimentally give people testosterone versus a placebo, then they're often impaired at recognising emotional displays in people's faces.

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Perhaps this helps explain why having high testosterone isn't good for your relationship. One study of over 4,000 men found that those with greater testosterone were less likely to get married, and if they did get married they were more likely to have affairs, to be psychologically remote from their wives and get divorced. The top 2% in the study were also twice as likely to be physically abusive towards their wives than the bottom 2%. It's popular to link aggression with testosterone, but the hormone is better understood as one of dominance.

Associate Professor Tom Denson
Dominance is trying to achieve a higher place in the hierarchy - more power, more status, more respect. In animals there's a very strong relationship between testosterone and aggression because that's how animals show dominance - they attack, they bite, they boss others around. In humans... we're a bit more complicated, so often you can exert dominance by forming coalitions and working in cooperative groups and acting pro-socially.

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In fact, a meta analysis of the relevant studies found almost no correlation between testosterone and aggression. Researchers suspect another hormone - cortisol - may help explain why. Cortisol is the stress hormone that motivates submissive or avoidance behaviour, such as trying to run away.

Associate Professor Tom Denson
Those two hormones interact, so if you have high levels of testosterone but you also have high levels of cortisol, it's possible that the cortisol could block the effects of the testosterone. But if you have low levels of cortisols, then testosterone can sort of exert its effects. And there were a couple of studies that were done with violent offenders, and they found out there was a relationship there between testosterone and violence and the severity of their crimes, but only for people who were low in cortisols.

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Professor Denson wanted to know if this modulating effect of cortisol was reflected in brain activity. So, he devised a devious MRI study. It analysed people's ability to control anger under the guise of an anagram test.

Associate Professor Tom Denson
So, what we'll need you to do is actually use all of the letters that you'll see in front of you to make a word.

Associate Professor Tom Denson
We create a situation where the participant is really motivated to control their anger - so, we have a very sweet research assistant who pulls the participant aside and says, 'Hey, look...'

Miriam Capper
Dr Denson's in a bit of a grumpy mood today. He's been getting upset with participants for not speaking loud and fast enough during the anagram task. We really need to make sure that you keep your cool during the task, otherwise the data will be completely worthless.

Kelvin Wong
Yeah, sure.

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The deception continued inside the MRI. First, Tom issued a few polite warnings.

Associate Professor Tom Denson
OK, we still can't hear you very well, so please speak up for me. Thanks.

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Then, he gave them a good telling off.

Associate Professor Tom Denson
Can't you follow instructions?

Associate Professor Tom Denson
I essentially say, 'Look, you're screwing up my experiment, can't you follow directions?' And essentially make them feel like a child and just treat them very rudely.

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For two minutes, the MRI analysed the regions of the brain that regulate emotion and control behavioural responses to impulses.

Associate Professor Tom Denson
So, what we see here is that these people that are high in testosterone and low in cortisol are actually showing inefficient functioning in this neural circuitry of anger control. So, they do want to control their anger and aggression, they're just not very good at it.

NARRATION
Just as we inherit an attribute like eye colour, we also inherit a level of testosterone that does fluctuate in the short-term. It's higher when you wake up than before you sleep, it goes up when you win and down when you lose, whether you're a player or a spectator. It falls when men marry or become fathers and increases when they divorce. But over a lifetime, the level spikes in adolescence, peaks in early adulthood and appears to fall with age. And losing it can affect a lot more than just your libido.

Professor Robert McLachlan
I think people often misunderstand testosterone as a sex hormone - 'All it does is about sex.' It's actually a hormone for good health in the male across life.

Professor Gary Wittert
If you look at men who are being treated for prostate cancer, and they get the production of testosterone switched off with a medication that stops it from being produced, that's not good for you.

Adjunct Professor Richard Wassersug
Typically, guys on androgen deprivation therapy lose about 3-4% of their muscle mass, which makes them weaker, but they gain about 10% of their body weight as fat, which makes it even more difficult. So, they're gaining weight but losing muscle, so there's fatigue, there's also increased risk of weaker bones - osteoporosis.

Professor Robert McLachlan
Their bones become very thin, very quickly. They'll lose as much bone in a year as perhaps a lady would across the menopause. So, that tells you what testosterone does, even in your 50s and 60s, to maintain your bone strength.

Professor Gary Wittert
They get metabolic abnormalities and they get accelerated progression to diabetes and a higher risk of cardiovascular disease.

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But any ageing man with low testosterone risks a similar suite of health problems, although to different degree.

Professor Robert McLachlan
Testosterone levels fall from middle-age onwards by about 1-2% per year, and many of us believe that the great majority of that decline relates to getting other conditions as you get older, particularly chronic diseases like obesity or diabetes.

Professor Gary Wittert
So, if you lose a lot of weight, testosterone will go up a lot, if you just lose a little bit of weight, from just a small change in your lifestyle, it will go up a little. But, of course, any little bit seems to help.

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This link lies at the heart of a major study led by Professor Gary Wittert.

Professor Gary Wittert
Look how much you've lost.

Neil Smith
Amazing, isn't it?

Professor Gary Wittert
Isn't it?

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He and his colleagues hope to recruit 1,500 men in five centres around the country.

Advertisement
So, you've hit your 50s and your six-pack is now a keg. You're not sleeping well, and you need to whizz in the night and you can't find your mojo when you need it most. Well, you might have low testosterone...

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Chris Baireuther was one of those who responded to the call.

Chris 'Bear' Baireuther
Everybody's who's getting a little bit older wants to find their mojo, don't they?

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The study is called 'T4DM', and the aim is to see if testosterone supplementation, combined with a lifestyle program of healthy eating and exercise, can prevent pre-diabetes from becoming diabetes, or, in new cases of diabetes, even overcome the condition.

Peter Pick
I was diagnosed by my doctor as I was pre-diabetic, and then I saw this online and decided to investigate it and joined up, basically, to find out a little bit more about myself and how I could hopefully arrest that blood-sugar level.

Professor Gary Wittert
We know that when men get overweight and pre-diabetic their testosterone level falls, but we also know that that low testosterone level in those men predicts the subsequent development of diabetes, irrespective of how it got low. So, the question then is, well, if that's the case, what's better - do you try and get people to lose weight, which is extremely hard to do, particularly men who might have, as a consequence of having a lower testosterone, which is loss of motivation. So, maybe the solution is to give these guys testosterone, combine it with a lifestyle program and test whether testosterone makes them more likely to comply with a lifestyle program.

Kim
Ten more seconds and then we've got another set.

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All the men are given free access to Weight Watchers...

Keith Spice
Green salad - six points.

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..and encouraged to exercise and eat well.

Dr Graham Phillips
What did 'Bear' used to eat?

Chris 'Bear' Baireuther
Eggs, steaks...

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Every three months they're given an injection of either testosterone or a placebo.

Dr Graham Phillips
What do you reckon? You think you're on the placebo or the real thing?

Chris 'Bear' Baireuther
I just don't know.

Keith Spice
I've lost 30kg in the last 14, 15 months and I feel absolutely fantastic. Everything that was wrong with me is virtually better.

Neil Smith
I feel energetic, I can do more things than I was doing before, and losing the weight actually gives you a lot more self-esteem as well.

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It'll take up to five years before the results of the study are known. Now, if low testosterone is bad for you, why doesn't every ageing Kelvin Wong just take a little more? Or a lot?

Professor Robert McLachlan
We don't know about its safety in older men who are not truly androgen deficient. There's a lot of promises made with not much evidence, and I think if you don't have the evidence you need to go get it, and that's, I'm afraid, the hard work of doing clinical research.

Professor Bu Yeap
If you're an older man, you get the best survival with a testosterone in the middle of the range. So, what you want is an optimal testosterone - basically, in the middle 50%. And you get the best survival with that.

Professor Gary Wittert
The notion that you should give testosterone back as the elixir of youth and vitality I think is still open to some question. And I know of no data to support the practice of doing that, particularly when the alternative, which is losing weight and getting fit, increases testosterone beautifully, and is absolutely proven to improve function, wellbeing and longevity.

Chris 'Bear' Baireuther
Health is a big thing. I mean, if you don't take care of your body, where are you going to live?