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BRITISH BROADCASTING CORPORATION
RADIO SCIENCE UNIT
CASE NOTES Programme no. 7 - Ovary
RADIO 4
TX DATE: TUESDAY 10TH FEBRUARY 2009 2100-2130
PRESENTER: MARK PORTER
REPORTER: ANNA LACEY
CONTRIBUTORS:
PETER BOWEN SIMPKINS
GORDANA PRELEVIC
USHA MENON
DR NARDO
PRODUCER: PAULA MCGRATH
NOT CHECKED AS BROADCAST
PORTER
Hello. Today's programme is all about the ovary. Over the next half an hour I'll be talking to one of the doctors behind early trials of a screening programme for ovarian cancer - a disease that affects around 7,000 British women every year.
We look at new tests to measure how fast your ovaries are ageing - and follow two women hoping they have not left it too late to start a family.
And I'll be finding out how to spot and treat polycystic ovary syndrome - a condition thought to affect at least one in 20 women in the UK.
STELLA
I have an obesity problem now but I didn't have it at the time when I was younger, I was just spotty and hairy and infertile.
PORTER
So you were quite slim?
STELLA
I was slim, yes, I didn't have that.
PORTER
You say spotty, hairy, infertile, I mean that's a pretty depressing triad.
STELLA
Yes it is.
PORTER
My guest today is Mr Peter Bowen Simpkins, a consultant gynaecologist and Medical Director of the London Women's Clinic.
Peter, let's start with the basics. What is the ovary and what does it do?
BOWEN SIMPKINS
Well the ovaries are the female gonads and they're the equivalent of testicles in men. And both have two functions - producing hormones and producing what we call gametes - in men that means the sperm and in women that means eggs.
PORTER
But the way in which they produce those is quite different because men carry on producing their eggs throughout their life but women don't do they.
BOWEN SIMPKINS
No that's absolutely right. Inside the ovaries are things called follicles and when a baby's born there are probably a million of those but by the time she reaches her puberty, say at 12 or 13, there may only be a 150,000 left and by the age of 50-52 they've all gone and that's what the menopause is. In any normal cycle about 10 or more follicles are stimulated and then one of them become dominant and it produces its own hormone, which knocks off the remaining ones. So the first one that reaches a decent size stops the other ones growing. So you may actually lose about 10 follicles per cycle but even so with - what is it - 520 cycles in your reproductive life that's still only 5,000 follicles.
PORTER
And the rest just whither and die?
BOWEN SIMPKINS
Yeah, they're just going all the time, like my brain cells.
PORTER
Thank you Peter, I want move on now to what happens when things start to go wrong.
At least one in 20 women in the UK have polycystic ovary syndrome or PCOS - a condition associated with three classic features. The women have an excess of male hormones or androgens causing acne and unwanted facial hair - hirsutism. They have multiple cysts on their ovaries and they have irregular or absent periods. And, to cap it all, they are often, but not always, overweight.
Dr Gordana Prelevic is consultant endocrinologist at the Royal Free Hospital in London and has a special interest in PCOS.
PRELEVIC
Young girls who come to see me at the age of 17, 18, 19 will always come either because of their lack of periods or unwanted hair growth. Then women who come at the age of 25, 30 would come if they don't have periods at all or because they're interested to get pregnant. And then later on, funnily enough when they hit their 40s, periods become more and more regular. I've been in this field for 30 years so had the advantage of following patients through and I actually see now some of my patients who had grossly irregular periods in their 20s and at the age of 45 they have completely regular periods. But then they start having problems which is high blood pressure, diabetes etc. So in adolescent years that is menstrual cycle problem and hirsuitism, then in 20s, 30s, it's infertility and then in 40s, 50s that is obesity, diabetes and high blood pressure.
PORTER
Stella has had PCOS for close to 40 years but at first her symptoms weren't taken that seriously.
STELLA
When I was about 14, so obviously around puberty I'd had two periods, I think, felt terribly grown up and then they stopped. So my mum took me to the doctor, GP, and he examined me and he said how long have you been hairy and I said well I don't know, I didn't really know. And he said I think you've got a hormonal problem. And he put me on the pill, he said that'll sort it out. Then we moved around quite a lot when I was in my early teens and again - and I started to get really bad acne. Every GP I went to, as we moved around Australia, said oh well it's one of those things, we're not sure what it is, but if you go off and have a baby that will sort the system out. And that was basically it for years until I ended up at Chelsea Hospital in London.
PORTER
What can you do to help them with their periods and their unwanted hair.
PRELEVIC
The treatment is basically symptomatic. You treat what is the main problem at that stage. So for treatment of hirsuitism that treatment has to be combined with mechanical removal of hairs. So - and I think that is very important for patients to understand and I often spend quite a lot of time in the first consultation. We don't have ideal treatment for hirsuitism, we use anti-androgens, which is a Cyproterone Acetate. So what can we expect from that treatment? We can expect that the hair growth will be slower, that eventually the new generation of hair will be finer, thinner, easier to get rid of but you cannot expect getting rid of all hairs. And because the hair lives quite long - as you know four to six months - it takes minimum six to eight months to observe any effect on treatment once you start somebody on anti-androgen treatment.
STELLA
You try to remove it, you try every hair remover there is, bleaching, I had electrolysis which didn't work because the hair growth, I was told by the electrolysis lady, that you ladies with hormone problems it never works for you anyway. And then I wanted to have a baby and of course I didn't ovulate.
PORTER
Because you still weren't having periods regularly were you?
STELLA
No I could go for months without one, never knew when they were going to turn up, which is also fairly inconvenient.
PORTER
So if you're using Cyproterone Acetate with the contraceptive pill or in the form of a contraceptive pill there'll come a time when your patients get to the stage where they'd like to try perhaps to start a family, so they obviously need to come off that, that's the first step, which then returns them back to the state where fertility may be a problem, what can you do to help them then?
PRELEVIC
First of all when they stop combined contraceptive pill a significant proportion won't have periods. And actually we know that out of those who present with so-called post pill amenorrhoea 60% have polycystic ovaries. First step is Clomiphene, which are tablets which are quite successful - induce ovulation. And then the next step, if that doesn't work, then the next step is induction ovulation with injections - Gonadotropin.
PORTER
And as a general rule, out of a hundred women who would come to see you complaining of infertility or sub-fertility, what proportion do you think you could help?
PRELEVIC
Almost everybody. I mean infertility associated with polycystic ovary syndrome is treatable, it is just a question of time and pursuing this.
STELLA
I'd had almost 20 years of fertility treatment and examination and photos and students looking at me and I got to a point where I thought I'm not going to take anything, I'm just going to just live with it and then I had a baby. It did seem to get a little bit better after that and it's got better since the menopause - the hair growth.
PORTER
Yes because you've been through the menopause now, so your ovaries effectively have shut down and they've had their day, has it made a noticeable difference?
STELLA
It's made a difference to the hair on the rest of my body, my face was more or less the same and in fact I asked the professor, who I see, whether there was anything she could do, even at this age, I wouldn't mind looking a little nicer and she's prescribed a cream and put me back on a very small dose of Cyproterone and it's worked like a charm. I have a friend who I met through a support group, an infertility support group, and I didn't have the obesity problem that a lot of girls have and this friend of mine had the lot, she had the hirsuitism, she was huge, the whole thing and I just think that must be so tough. I have an obesity problem now but I didn't have it at the time when I was younger, I was just spotty and hairy and infertile.
PORTER
So you were quite slim?
STELLA
I was slim yes, I didn't have that.
PORTER
You say spotty, hairy, infertile - I mean that's a pretty depressing triad...
STELLA
Yes it is.
PORTER
.... for a young woman.
STELLA
It is, it's very depressing. I mean now I'm much more secure in myself, I'm older, I've been through life, I've had my baby and it's not nearly as daunting. But I really feel for young girls who are just diagnosed with this, I'm so glad that there's a charity that helps, support group, which there was nothing like that in my day. And also doctors understand it and say well yes you have this and they can scan your ovaries now and have a look. So life is better.
PORTER
Stella, talking to me at the Whittington Hospital.
Peter, what's actually going wrong in the ovary?
BOWEN SIMPKINS
Well that's quite a complicated question and not one with an easy answer. What we do know with these women is that they become resistant to insulin, you know that's the hormone that governs your sugar levels, rather like people who get late onset diabetes. And these high insulin levels they've got circulating has a direct effect on the ovaries and it upsets the balance of the way the hormones come out and you get an excess, particularly of, and this is rather surprising, testosterone, which is a male hormone.
PORTER
It might surprise listeners that women produce testosterone but they do normally don't they.
BOWEN SIMPKINS
Oh absolutely but fortunately they produce another hormone, which is called sex hormone binding globulin, which is like a big mop and it goes around mopping up all this testosterone. And unfortunately in people with polycystic ovaries those levels may be very low so the amount of testosterone they've got is in effect much higher than in normal people and that's why they get this unwanted hair growth on their face, their chest, forearms, legs and so on.
PORTER
What's the link with weight? Traditionally I think of many women with PCOS as being overweight.
BOWEN SIMPKINS
Yes, I mean as you heard just now it's not necessary that people should be overweight but it is very commonly associated and it's a bit of a chicken and egg story because if you're very overweight the fat actually produces oestrogen and the oestrogen has an effect again on the pituitary gland which increases the amount of luteinising hormone, which is the one that makes you ovulate. But the levels are deranged and there's too much of one and not enough of the other. So these people tend then to develop polycystic ovaries and produce then the excess amount of testosterone.
PORTER
So they're caught in a sort of vicious circle.
BOWEN SIMPKINS
Exactly and that's the problem and one of the ways of breaking the cycle - and I do appreciate and people listening who have got this will tell you just how hard it is - but losing weight really is one of the major ways of dealing with the situation.
PORTER
I mean in terms of looking at symptoms, if a woman was to have problems with her periods say and she was to lose weight could she actually restore a normal cycle?
BOWEN SIMPKINS
Yes certainly. I mean one of the main things we really do try and attempt is to get people - to get their BMI, their body mass index, down below 30. I mean the normal range is about 19-25 but below 30 usually their periods will return.
PORTER
What about the implications for general health? You mentioned there that this is - PCOS is related to insulin resistance which we know is also related to type 2 diabetes, are there long term implications for women's health if they have PCOS?
BOWEN SIMPKINS
Well certainly the ones who are overweight, it can lead to raised blood pressure, diabetes as you heard, and those two in themselves can lead to coronary heart disease, so early heart attacks, and also the fat - the cholesterol levels - in the blood tend to go up which again increases the risk of heart attacks. Interestingly one of the drugs that we use for type 2 diabetes, called Metformin, has been used quite a lot in this condition and certainly does seem to return periods for those who are sub-fertile.
PORTER
So if you have PCOS then you should know your cholesterol level, and have your blood sugar and blood pressure checked regularly.
Now we have already heard that women are born with a finite supply of eggs that age with them - unlike men who continue to manufacture fresh sperm throughout their lives. Or to put it another way, the ovary is a warehouse while the testicle is a factory.
But as more couples put off starting a family - the average age of women having their first baby in the UK is now around 30 - a growing number are worried about leaving it too late. One way to avoid that is to have your ovarian reserve assessed - a measure of your biological age and the chances of conceiving.
Our reporter Anna Lacey went along to the SMS Women's Health Clinic in Harley St to meet two women keen to find out what state their ovaries are in. Sally is a career woman in corporate sales who will soon be turning 36.
SALLY
I do have three or four couples of friends that are trying to have children at the moment and it just made me think more about my age and just decided to research myself on google and literally just typed in ovary testing and their clinic appeared.
LACEY
So can you just tell me a bit about what happened when you came to the clinic, what kind of tests did you go through?
SALLY
I first had a blood test and then I went on to have an internal scan as well.
LACEY
And what were the results from your tests?
SALLY
My results came back as satisfactory, so middle level really for my age.
LACEY
It's not just women in their mid-30s who want to know if their ovaries are ageing. Twenty nine-year-old Karen lives in West London and has been trying - unsuccessfully - to get pregnant for the past year. She went to a consultation to talk about her circumstances.
ACTUALITY
DOCTOR
Hello Karen, nice meeting you.
KAREN
Hi, nice meeting you.
DOCTOR
Come and take a seat.
KAREN
Thank you.
DOCTOR
I understand you tried to get pregnant.
KAREN
Yes.
DOCTOR
And have you ever been on the pill?
KAREN
Yes I've been on the pill for quite a lot of my life.
KAREN
I decided to come for the test by recommendation of a doctor. I'd been through a lot of chemotherapy and other problems when I was a child and always knew, in the back of my mind, that it might not be possible for me to conceive in the future. So we decided to try for a baby. The first thing we did was we came off the pill and as soon as I came off the pill my cycles were completely all over the place. One month I had two and the next six months I didn't have any and then they came back again and they kept coming and going for quite a while, so I knew something was up and that's when I went back to the doctor to say look something's not right can I find out more.
ACTUALITY
DOCTOR
And have you got regular periods now?
KAREN
No they're quite irregular at the moment.
DOCTOR
When was your last period?
LACEY
The ovaries are assessed in two ways. The first is a simple blood test which looks at the level of a chemical called anti-mullerian hormone or AMH. It's produced by the ovaries and gives a good indication of how many eggs a woman has left. The second test uses ultrasound to count the number of immature egg follicles - also known as antral follicles - on the surface of the ovary. Dr Nardo looked at Karen's AMH results.
NARDO
Well the AMH was very low, it came back 0.6, the optimal fertility range, just to give an idea, is between 28.6 and nearly 50. And AMH levels below 2.2 come within the very low undetectable fertility.
KAREN
The doctors have always told me that it might not be possible, so I was always prepared for the bad news. The next step is the internal probe and hopefully that will give me more details as to what the next step is and how far to go.
ACTUALITY
NURSE
Are you okay with latex?
KAREN
Yes.
LACEY
So now Karen, she's lying on one of the beds here and Dr Nado's just preparing for the scan. So can you just describe what you're going to do now?
NARDO
We're going to do a trans-virginal scan which involves inserting a fine probe into the virgina in order to visualise the pelvic organs which are mainly the uterus and the ovaries.
LACEY
Okay so this probe here it just - well it just looks like a long plastic probe, maybe a couple of centimetres wide, and he's putting something that looks rather like a condom over the top.
NARDO
Okay, so we are about to perform the pelvic scan. Karen, try to relax.
LACEY
So what we've got here is a big machine and a screen and on to the screen now - well we can see quite a lot of grey and white but I can't tell you what this is, so Dr Nardo what's this?
NARDO
Well we can visualise the uterus and I can see the left ovary, which I'm going now to measure. There - the ovary has an oval shape and the ovary contains small follicles, unfortunately no follicles are visible on this occasion.
LACEY
So what does that mean then for Karen's ovaries as a whole?
NARDO
Well unfortunately this is in keeping with the AMH results, suggesting a very low fertility.
LACEY
Even with this news, Karen still has a chance of falling pregnant with the help of egg donation. However, despite their different results, both women said they felt better knowing for sure about their ovaries, rather than making a guess based on age.
SALLY
When me and my sister had talked about things a few years ago it was would you like to know, would you not like to know, would you just like to get on with it and just see what happens. Well I think deep down you do really want to know what your chances are.
KAREN
Yeah that's why I decided to go for it, I mean they always say never say never, go for it and find out. There might be that small chance that I still can, so I'm going to find out more.
PORTER
Karen and Sally talking to Anna Lacey. You are listening to Case Notes. I am Dr Mark Porter and I am discussing the ovary with my guest consultant gynaecologist Peter Bowen Simpkins.
Peter, when does the waning fertility start to become critical?
BOWEN SIMPKINS
Well roughly speaking it becomes critical about 10 years before the natural menopause. Now for the average woman that's 52, so at the age of 42 most women's fertility starts dropping off. That doesn't mean to say that they can't get pregnant because any woman who's having regular periods can get pregnant even at the age of 50 but it becomes less and less likely.
PORTER
And that waning fertility is due to what - is it simply the quality of the eggs, that the eggs are getting too old?
BOWEN SIMPKINS
Yes probably, they don't fertilise as well, the miscarriage rate goes up really very, very rapidly and we know that at least 60% and probably even more in the older woman their chromosomal abnormalities, in other words things going wrong actually inside the ovary and they never fertilise properly.
PORTER
We heard there that Karen had had chemotherapy as a child, are there things that we can do now to protect fertility in these type of women?
BOWEN SIMPKINS
Well in young pre-pubertal children chemotherapy's not - if it's going to destroy ovary function it will and there's not anything you can really do about that. Many people have to have radiotherapy and in those cases you can shield the ovaries. What we see mainly in our unit are women who are teenagers and who haven't had a family and are going to have to have radiotherapy or chemotherapy and in those cases we can harvest eggs from their ovaries - we stimulate the ovaries and take as many eggs out as we possibly can. And they can undergo a process which is called vitrification, which is a way of freezing them, and then they can be kept as long as necessary until such time as they - they have a stable partnership and want to have a baby.
PORTER
And what sort of success rate would you have re-implanting those?
BOWEN SIMPKINS
Well this particular process of vitrification has only really become a big thing in the last eighteen months to two years. At present we're getting about 60-80% of our vitrified eggs survive thawing and then of course the chances of pregnancy are whatever that particular clinic has. On average in the UK for women under the age of 35 it's around about 35%, others is even higher than that - we're running just over 50% now.
PORTER
Well another thing that can happen to the ovary as it ages, is that it can turn cancerous. Ovarian cancer is the fourth most common cancer in women and is responsible for close to 5,000 deaths every year in the UK.
It's a difficult condition to diagnose as the symptoms tend to be vague and are easily confused with much more common complaints like irritable bowel syndrome or urine infections. A difficulty compounded by the fact that a typical GP will only see one case of ovarian cancer every five years.
Usha Menon is Head of the Gynaecological Cancer Research Centre at University College London.
MENON
At the moment most of the women are presenting after the disease has spread beyond the ovaries, so in stage three and four as we describe it. And treating the disease in that stage is difficult. There is a query as to also whether there are two types of ovarian cancer. One type which is more aggressive, so that in that type of ovarian cancer, even if we caught it early, it would come back.
PORTER
And who are these women, what sort of typical presenting patient look like?
MENON
Really most of the women come from the general population and by that I mean they don't have a family history of ovarian cancer. So 90% of the women belong to this group. They're usually over 50 and mostly post-menopausal, so their periods have stopped and there are some risk factors which sort of increase the risk slightly and those are not having children, not having used the pill at all and some factors decrease risk - like having used the pill or having had a hysterectomy or your tubes tied. Ten percent of the women are high - what we would describe medically as high risk women and by this we mean they come from a family where this is an increased number of women with ovarian cancer or with breast cancer at a young age.
PORTER
How do we think the protective effect of the contraceptive pill is working, what's it doing?
MENON
The sort of standard long term view is that it's because it protects the ovary by preventing ovulation. During ovulation there's a little break in the ovary because the surface of the ovary has to almost like rupture to release this egg and so there's a little injury on the ovary and there's recovery, so there is the usual process of healing and this happens repeatedly and during these cycles perhaps one of the cells gets a little abnormal and then goes down a pathway after many years.
PORTER
What about symptoms - how might a woman know that she was developing cancer of the ovary?
MENON
So the issue with symptoms is they're not really gynaecological symptoms. They're more abdominal symptoms. Persistent pelvic and abdominal pain, increase abdominal size or persistent bloating, so not something that comes on and off which many women might experience but something that persists over two, three weeks. And the other symptoms - difficulty eating and feeling full quickly. So these - it's not that these are the only symptoms, there are a number other symptoms which in the early stages - which might be present like urinary frequency. But the most important thing is for women to know their body and to know the change in the symptoms because they're fairly common, so the change in symptoms which was for a long time.
PORTER
But this is one of the problems, isn't it, with cancer of the ovaries they are quite vague symptoms and perhaps not taken as seriously as they should be, either by the women or by their GPs ...
MENON
Absolutely Mark, I think that is the big issue and the question is how to get round that. And that is why now the Department of Health has a huge cancer awareness programme out for all cancers and they're trying to see if the increase awareness of these symptoms and that is why we're trying to kind of bring these symptoms out in the open. But you are totally right that they're most likely due to a host of other issues rather than ovarian cancer.
PORTER
Now one of the areas that you're working on is looking at the benefit of a screening programme. We have obviously screening programmes for breast cancer and for bowel cancer now, would it be feasible to do blood tests and scans on women perhaps at high risk to start with?
MENON
It seems feasible because you know we've got two research trials running in the UK, national research trials, and one in 200,000 women, which is a general population trial, and one in - the aim is 5,000 - and at the moment there are about 4,000 women in that trial in the high risk population. In both groups women seem to be willing to come year on year to have the blood test or the scan and we seem to be able to manage the logistics. So logistically it's feasible, the question is will it make a difference?
PORTER
What are you looking for in a blood test?
MENON
So in the blood test we are looking for a substance called CA125, it's a substance naturally produced in the body but in ovarian cancer the substance is produced in larger amounts and we're looking for a change in levels.
PORTER
So that combined with a scan to actually visualise the ovary would mean that you could pick up a problem - how early on in the disease?
MENON
Now this is the question that is being answered at the moment. There's no question that there have been lots of trials and we ourselves have done work before the - we will pick up women before they are aware that they have ovarian cancer, the key question is how early, is it early enough and for that really - for me to really answer that question we do need to wait till this big trial of 200,000 women completes. The women are having screening till the end of 2011, the plan is at the end of that the 100,000 women who did not have any intervention we would count the number of women who died of ovarian cancer in that group versus the women who had screening.
PORTER
So this 200,000 group is split into two?
MENON
That is correct.
PORTER
One who'll have something done, one who don't have anything done?
MENON
That's absolutely correct. And if we could find - show that there is a difference - screening makes a difference we can pick it up early enough so that the women recover and they don't succumb to the disease then I think the government would be persuaded to have a programme.
PORTER
Usha Menon. And I'm afraid we must leave it there. Peter Bowen Simpkins thank you very much.
I will be swapping the confines of the studio for the open roads of Gloucestershire for next week's programme, when I find out what's in day's work for the paramedics.
ENDS
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