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Premenstrual Syndrome. -

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Dr Jonica Newby reports on a new therapy for women who experience difficulties due to PMS. The
recent discovery that the monthly fall in progesterone levels are accompanied by a rise in the mood
changing hormone allopregnanolone, has led to a new way of taming the monthly monster - by the
controlled administering of a commonly prescribed antidepressant.

NARRATION

Does this sound like you or your loved one - lovely woman, kind to kittens, but once a month,
replayed by evil twin.

Dr Jonica Newby

So what's the worst thing you ever did with PMS?

Woman

I remember I sort of smashed the bannisters, because I was ...

Dr Jonica Newby

Smashed the bannisters?

Woman

Yeah, I was really frustrated about something.

Woman

Mobile phone.

Woman

Photograph.

Woman

Ah ... cups, plates, ah ...

Young man

She just moons all the time.

Woman

Ripping out a kitchen. Does that count? The whole kitchen - plumbing, cooker and everything. So now
I have no water, no cooker, or anything.

Dr Jonica Newby

For something that's so common and so potentially destructive, I can't believe how little science
has looked at pre-menstrual syndrome. But I'm pleased to report that's changing.

NARRATION

Which is why I'm here in Birmingham, to find out what goes so wrong in the brain once a month, and
how potentially to fix it.

This is Birmingham University, where I'm getting ready to meet some rats, with PMS.

Dr Jonica Newby

How can you tell ...

Dr Thelma Lovick

Well ...

Dr Jonica Newby

Don't tell me - they act a bit ratty?

Dr Thelma Lovick

That's really bad. No, what we do, is we put them into a situation where they're slightly stressed.

Dr Jonica Newby

Yeah?

Dr Thelma Lovick

Then we have a look and see what they do.

Dr Jonica Newby

Alright. Shall we?

Dr Thelma Lovick

Yes.

NARRATION

Rats prefer small, dark places. So to explore, they have to brave an open space. Fine on a good
day. But when they're pre-menstrual, well, as Thelma found, they just want to stay in.

Dr Jonica Newby

So once a month, they just go, 'Ah!'

Dr Thelma Lovick

Oh, once every four days in rats.

Dr Jonica Newby

Once every four days. A period every four days, how do you like that? I'm glad I'm not a rat.

NARRATION

In fact, rats don't get periods. But they do have a similar hormonal oestrus cycle, which meant
scientists like Thelma at last had a way of seeing what happens to female hormones inside the
brain. We've long known falling progesterone precedes PMS, but we didn't know is that the real
culprit is its breakdown product, Allopregnanolone, or ALLO for short. So here's what we now know
can go wonky once a month:

Dr Jonica Newby

So we're inside your brain now, this is a nerve ending, and these are all your stress responses -
the chemicals that ramp up your emotions. Now normally they have a dampener on them. An inhibitory
chemical called GABA. And here comes ALLO, ALLO helps GABA, just keeps everything calm.

And then, once a month, just before your period, progesterone drops. So ALLO suddenly drops, GABA
has to struggle all on its own, and then all of a sudden, there's nothing keeping those stress
responses in check.

NARRATION

In other words, the brain's emotional responses are briefly primed to over-react - fight or flight,
anger or deep depression.

Dr Thelma Lovick

We become hyper-responsive to quite trivial stress.

NARRATION

And in some women, the over-reaction is extreme.

Debbie Dawson

We had a dinner party, and we were clearing the table, and he was starting to put things in the
dishwasher. And I said to him, 'I'll sort the dishwasher out,' because it is a common fact - we all
know that men can't load dishwashers. And he carried on, and I was getting really angry. So I just
picked up the nearest thing, and I just threw it at him. Ah, and it literally skimmed his ear, and
stuck in the washing-up bowl. He looked back, you know and you think God, that was, that could have
been really, really dangerous.

NARRATION

Debbie Dawson runs her own hairdressing salon. But not long ago, she was so close to losing
everything.

Debbie Dawson

Fell out with a lot of people, fell out with family, fell out with friends. Horrible things coming
out of my mouth. But there was no remorse. I didn't, wasn't really bothered that I was being
horrible.

NARRATION

How many times do I have to tell you? I tell you over and over and over ...

While fifty per cent of women get multiple PMS symptoms, around five per cent get disabling PMS -
mood swings so serious they're categorised as PMDD.

Professor Susan Davis

Come in.

Dr Jonica Newby

Thank you.

NARRATION

And if they're lucky, they eventually find their way to someone like hormone specialist, Professor
Susan Davis.

Professor Susan Davis

Okay, so the question is ... A lot of the women I see are very extreme cases, because often they've
seen a number of different health-care professionals before they get to me, and they're at their
wit's end.

Dr Jonica Newby

Some PMDD sufferers have even been misdiagnosed as having depression or bipolar disorder.

Professor Susan Davis

I think people have trivialized in the past hormonal problems in women. I think also what happens
is that a lot of women do deny that this is happening to them. And it's only when something really
catastrophic happens, when they pick up a child and shake their child, that they realize they have
to actually do something.

NARRATION

Debbie still had no idea what was wrong when her second husband told her he was leaving. And
finally, someone referred her to a gynaecologist.

Debbie Dawson

I was only with the gynaecologist twenty minutes, and instantly she said, 'I know what's wrong with
you.' And of course then, I sat when I got home for hours, going back over four years of diaries,
and the pattern was unbelievable. You know, I could turn the page and know I'm going to say on this
page I was evil, turn the page and there it was - evil, literally a week before my period.

NARRATION

It was a startling revelation for her, but what she decided to do about it will startle you even
more. She decided to have her ovaries removed, and the hormones along with them. But if scientists
are getting new insights into what's causing the monthly madness, is it opening up new ways to fix
it?

Dr Thelma Lovick

Now I thought, when ALLO falls in the brain, what if we could give a drug that would raise it
temporarily. And then in the literature, I came across a really, it was a really exciting fact,
that the compound called Fluoxetine which is really a very well-known anti-depressant, has property
of raising brain ALLO levels. And it does it very quickly.

NARRATION

You know this drug, it's Prozac. In fact, Prozac has been prescribed for PMDD for years. Indeed,
our bannister-smashing friend was put on it. But there are some serious side effects, not least of
which are personal.

Woman

Kills your libido. Yeah, my husband would get a bit upset.

Professor Susan Davis

About forty per cent of women treated with anti-depressants will experience loss of libido, loss of
arousal, um, loss of ability to have an orgasm.

Woman

But I just thought, well I'm better off to be a reasonable person for sort of twenty-seven days of
the month than you know, be able to have sex a few times, a few times, you know.

NARRATION

But here's what's so neat about what Thelma tried. She delivered the Prozac at a twentieth of the
normal dose, and only on the day her rats normally got PMS, and completely prevented their
symptoms. Even more exciting, the dose was so low, it wasn't even affecting serotonin, implicated
in depression.

Dr Thelma Lovick

I don't think it's treating the depression at all. And the reason for that is that the dose of
Fluoxetine that we need to raise brain ALLO levels is about a tenth of the dose that we need to
affect the serotonin systems. And of course, at such low doses, of course it should be very, very
safe.

NARRATION

Meanwhile, over in Melbourne, Professor Davis has already been experimenting with intermittent
doses a quarter of those recommended for PMDD, and it usually works.

Professor Susan Davis

To general practitioners watching this, I'd be saying um, don't give up. Try using the lowest dose
you can titrate down to. So the lowest dose you can break the pill into. And see if you get a
benefit with that.

NARRATION

And what about Debbie, who'd taken the extraordinary step of having her ovaries and uterus
surgically removed?

Debbie Dawson

By the time I came out of hospital, I felt a different person. It was overnight, literally. It was
unbelievable. It was like the end of a long, long period of heartache really, had come to an end,
literally. Yeah, it was brilliant.

Dr Jonica Newby

We're all different, and there's never going to be a one-size-fits-all solution. But the more we
understand about the physiology of PMS, the better chance we'll have of putting the lid on that
monthly madness.

Topics: Health

Reporter: Dr Jonica Newby

Producer: Dr Jonica Newby

Researcher: Roslyn Lawrence, Dominique Pile

Camera: Scott Munro

Greg Heap

Sound: Rob Eade

Adam Toole

Editor: Chris Spurr

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