In men with prostate problems flutamide works as follows:

The easiest way to understand the way flutamide works is to liken the process to that of a lock and key. On the surface of the prostate cancer cells, there are proteins called receptors. The receptors are the lock and testosterone is the key. When testosterone comes into contact with the receptors it fits into the lock and activates the cancer cells to divide, so the tumour grows. Flutamide imitates the action of testosterone and fits into the lock but the key does not turn and the cells do not divide. The flutamide remains in place and prevents the testosterone from reaching the cancer cells so they either grow more slowly or stop growing altogether.

Now if this action prevents testosterone from reaching cancer cells, the same drug in a child with CAH will prevent any testosterone released from reaching the cells it is meant to reach also.  In fact common side-effects of flutamide in men are:

Breast tenderness or fullness. Some men may notice slight breast swelling and tenderness. Your doctor can prescribe medication to reduce any discomfort.

Diarrhoea. This occurs quite commonly and may be accompanied by abdominal cramps. Diarrhoea can usually be easily controlled but occasionally it may be severe. It is important to inform your doctor if this occurs as they may feel it is necessary to reduce or discontinue the flutamide, and consider other types of hormonal therapy.

Nausea (feeling of sickness) or vomiting. These are uncommon but may occasionally happen. If they do occur they can usually be effectively treated. Tell your doctor if you have nausea or vomiting. CancerBACUP’s booklet Diet and the cancer patient discusses ways of coping with these effects.

Lowering of libido (sex drive), and impotence (a loss of ability to have an erection). This is an uncommon side effect. If it occurs sexual function will return to normal after stopping the drug. Your doctor or nurse can discuss this with you. More information is available in CancerBACUP’s booklet Sexuality and cancer.

Tiredness. You may feel less energetic than usual and it is important to take time to rest. This usually subsides when the flutamide treatment is stopped.

Effect on liver function. Your doctor will take blood samples to measure your liver function as flutamide can sometimes cause the liver enzymes to become abnormal. If this happens the drug will be stopped and the liver function usually returns to normal.

 

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You say that the point of the NIH study is to use an anti androgen such a flutamide and that this is meant to LOWER androgen production, but to allow levels to be higher.  As far as I knew flutamide blocks androgen to varying degrees does it not?  Some cases what androgen there is could be in fact much lower androgen levels than there should be for that child at that time.  How do you lower something to the exact degree if you don’t know exactly what should be happneing for that child exactly at that time in relation to their other hormones levels?   Even if you drop the cortisol dose down to a minimum and block excess androgens, to what extent have you blocked them.  A smidgen?  A Lot? Totally?  I’d say that the dose determines that to be honest, and especially when it can cause problems varying from merely loss of libido to full blown erectile problems in men whom use it.  Some may be ok with a certain dose, others may be totally dysfunctional at the same does.  This means tweaking the dose.  I would jolly well hope so anyway especially in children who are dependant upon androgen not just for libido but more importantly a growth spurt.    I merely mentioned that it is going to make it more difficult to determine the dose in conjunction with what is happening growth wise.  They are not going to be able to get this dose or level  to get this "level" spot on the first time.  In some case there may be too much androgen because there isn’t enough flutamide and vice versa.  Also children will out grow the flutamide dose at varying times and it will not be enough, thus rendering them exposed to much higher androgen levels than should be-----and this is no different to convetional treatment in that respect then is it?     To me this just illustrates that the same thing can happen with that treatment as what can happen without it.  The point of making things more complicated with two more drugs therefore was? 

If flutamide was not good at blocking androgen or testosterone in men with prostate they would not use these drugs at all because the point of men with prostate using this drug is to reduce test permanently.  The problem is, they are no more clever at controlling the level of testosterone that these men are exposed to and the dose of flutamide for each guy as what they are at NIH so subsequently some receive the dose and have unpleasant side-effects and others don’t even notice.  Some may just have a loss of libido, other’s may be over treated and have a total loss of libido and erectile dysfunction.  So you can assume further to that that different children will need different doses of flutamide at different stages and of course this means tweaking the dose as I said.  In other words one more drug to tweak and one more drug that will effects side-effects if it isn’t tweaked right. 

Also, if they get the testalactone dose wrong then this can effect side-effects also i.e.  the blood glucose is high and growth doesn’t occur.  Yet another drug to tweak which carries potential side-effects that can occur either way if they don’t tweak the dose right. In fact BOTH of these would have to be tweaked as the child grew and the androgen levels needed to change at varying stages of their childhood.  Anyone knows here that androgen and estrogen levels are different for boys and girls of different ages.  They will all be at different stages at different ages, and one does of either of those that does not "shift" with them in that change will eventually cause problems such as in the boy above.  For example he could at his age need a higher androgen levels than is present.  However they may have him on too high a dose of flutamide which is suppressing androgens too much for growth to take place at his age.  These children in that study are going to have to have gone through every age and stage and have their treatment grow with them successfully right into adulthood  before anyone can look at the stuidy and say it was far easier than controlling kids on conventional therapy.  Or even worth risking the side-effects of the addictional drugs for children in order to squeeze another few inches of height out of them.   Any drug not controlled properly will cause side-effects.  Flutamide and testalactone are no exception.   

As you all know there is a negative feedback mechanism where most hormones we are talking about are concerned... in other words some other hormone is released at some point when another is too low or too high.  This causes balance amongst them all.   This means at any one time there is a perfect balance struck between what is happening and what needs to happen.  However, in the case of the children above, they are changing the levels of one and elevating others and not necessarily in harmony with eachother either in fact it could be in total cacophony with the way things should be, which all has just as much potential to cause OTHER hormones to be released in excess and cause side-effects as conventional treatment does if not a few more than we are already familair with as of yet with conventional treatment.     The fact that I pointed this out in my opinion is not bad here Toni.  

There seem to be much more room for errors to occur amongst a cacophony of four drugs inappropriately controlled, than what there would be for children whose parent’s have accepted what has happened for them and just control the two hormones that are not being made correctly.  The fact that some Doctor’s can’t do this properly just means one thing to me.  More Doctor and patient education is needed in how this should be done instead of arguing about it.  

I.e How control should be done correctly, how often tests should be, what normal reference ranges should be etc etc.  The fact is it varies so much, no kid’s Doctor treats this condition alike and it is for that reason only that conventional hormone replacement of the missing hormones effect side-effects on occasion here.  Not the fact that the drugs don’t work for goodness sake.  At some stage even if this treatment is approved your going to get Doctors disagreeing with how it should be done and some kids having more serious side-effects than just conventional treatment can effect.  In other words, as hard if not harder to control than they are now. 

So at this stage you’ll have to forgive me if I disagree with the drugs used or feel that the NIH study complicates the matter one step further where treatment is concerned, but we are all entitled to study these things and form an opinion without criticism.  I’d like to think we could post them too without being made to look idiotic at times.  Parents using their noggins and moving further ahead and studying this and speaking thier thoughts on what the potential hazzards are is what this board is all about isn’t it?  It is to be applauded IMO not criticised.  Otherwise how the heck does anyone here compare apples with apples and get to the truth?  Should we have big brother dictating how it’s to be or can we think for ourselves occasionally?  I’d like to think so...  We all are supposed to be exchanging thoughts and ideas, not being damned for it.  If my thought processes went off in a different direction, I’d say it is a good thing not a bad one.  We don’t all think the same and that is positive not negative IMO.