The steroids are a large group of chemicals which share a common basic structure. At the head of the group lies cholesterol. Our bodies can store and make large quantities of cholesterol, using it to produce many different steroids, without which we would not survive.

Most of the body’s natural steroids are hormones, (chemical messengers) which control many of the body’s basic functions. There are two main types of steroid hormone. The first is the sex hormones, oestrogen and progesterone in women and testosterone in men, which are critical in the development of our sexual characteristics. Without them we would be sterile. The second group are made by the adrenal glands which lie next to the kidneys. These adrenocortical hormones play a vital part in the body’s metabolism, controlling the way the food we digest is processed providing the energy we need to think, move and grow. They are particularly important in controlling the balance between using the food immediately and storing it in the body as fat, for later use.

Another major role is in the control of the body’s water content. Steroids stop us from drying out in hot weather, ensuring that the body holds on to the water we drink to replace sweat and urine. Moreover, steroids are important in controlling the correct balance of salts in the blood.

The adrenal steroids have several other less well understood functions. For example, they can influence mood, behaviour and brain excitability. Patients with a condition called 'Addison’s disease', in which the adrenal glands stop making steroids, are often apathetic, depressed and irritable. On the other hand, patients with 'Cushing’s disease', in which the adrenal glands produce excessive amounts of steroids, are often excitable and euphoric with hallucinations and delusions.

In healthy people the level of these steroids in the blood varies through the day, being highest on waking and lowest at night. This has led to the suggestion that they may be important in getting us going in the morning whilst letting us wind down at night. Steroids are almost certainly essential for normal bone marrow functions - patients with Addison's disease are usually anaemic.

Steroids may also affect the immune system, that is the body's defence against infection.  However, in this case they seem to be suppressive, in that patients with Cushing’s disease and excessive steroids are less able to fight infection.  It may seem surprising that the body makes substances which reduce its defences but the control of the immune system, like all the body's basic processes, is a finely tuned balance of forces.  It is just as important not to over-react to an infection and risk damaging the body with your own weapons used in self-defence as it is to under-react and let an infection take hold.

So  the body’s natural steroids are potent and vital chemical signals. It is essential that their levels within the body are strictly controlled to the amount required for best function, no more and no less. This control is exerted by the body’s 'master' gland, the pituitary. This hazelnut-sized gland sits at the base of the brain and monitors the function of most of the body’s hormone-producing glands, including the adrenals. It can detect exactly how much adrenal steroid is in the blood and knows whether or not the level is correct. If there is too little the pituitary sends out its own chemical signal which tells the adrenal glands to make more steroids.

When the pituitary senses the correct level it stops signalling and the adrenal glands temporarily switch off. If left undisturbed by disease or medical treatment this 'negative feedback' control system functions throughout life to keep our body’s biological processes in balance with its everyday needs.

For many years, doctors have had steroids available and they have turned out to be a considerable help in many diseases.

Different types of steroids

In fact, doctors prescribe all kinds of steroids, such as the sex steroids oestrogen and progesterone in contraceptive pills and hormone replacement therapy. Hormone treatments are also important weapons in the fight against breast cancer.  'Anabolic steroids' (male hormones) are the ones that athletes are occasionally found taking to increase their muscle strength.

In treating lymphomas and leukaemias we use drugs which only look like adrenal steroids so we are not in the business of producing weightlifters! A general term for this group of drugs is corticosteroids, the most common ones being dexamethasone, hydrocortisone and prednisolone but there are several others. Although produced artificially, all of these have the basic cholesterol steroid structure.

When you are given corticosteroids, either as tablets or by injection, your own pituitary is fooled into believing that the body is making more than enough adrenal steroids and so it switches your own adrenal glands off.

They stay switched off for as long as you take corticosteroids continuously. If this extends for many months the adrenal glands shrink ('atrophy'). If you then suddenly stop taking the corticosteroids the pituitary gland senses the lack of steroids immediately. However, if the adrenal glands have shrunk, no matter how hard the pituitary signals they may not be able to resume normal hormone production straight away. Without any steroids, artificial or your own, you would be in danger of becoming seriously ill.

This is why patients on steroids should always carry a warning card (it's usually blue), so that if they are admitted to hospital unconscious the doctors know they must be continued on these drugs. It is also why at the end of a course of treatment steroids are often tailed off, by gradually reducing the dose over days or weeks. This allows the adrenal glands to 'wake up' gradually so that when the tablets are stopped they can resume their normal function. To be safe the card should be carried in your handbag or wallet for 18 months after your steroid course has finished.  If you have an operation during this time you must show the card to the anaesthetist.

One way of getting round the problem of the adrenal glands shrinking is to give steroids in short bursts such as for five days every few weeks, or on alternate days if they are to be continued for several months. Both these patterns of administration are used in certain chemotherapy regimes for lymphomas and leukaemias, so avoiding the need in some patients to 'tail off' the dose after the end of treatment.

If a patient takes high doses steroids for many weeks they begin to look like someone with Cushing’s disease. Steroids markedly stimulate the appetite, so patients eat more and put on weight.  The patient will tend to put weight on around the face and trunk but lose it from the arms and legs. This gives the characteristic 'moon face'. This change of fat distribution simply reflects the normal role of adrenal steroids in controlling the handling of food stores. Our natural steroids act to raise the level of glucose sugar in the blood, whilst the (non-steroid) hormone insulin acts to lower it. The balance of these influences keeps it on an even keel. Disrupt the balance by overpowering the body’s insulin with excess steroids and the glucose levels can rise so some patients on corticosteroids develop higher levels of sugar in the blood. The name given to the condition in which blood glucose levels are too high is diabetes and steroids can produce this in some people - though it is usually temporary. Symptoms to look out for are thirst, passing lots of water and infection, especially thrush (see later also). Obviously, giving steroids to somebody who is already diabetic is a complicated matter though by no means insurmountable - many diabetic patients have been treated successfully for lymphoma - including the use of steroids.

So far we have seen how the side effects of corticosteroids are simply an exaggeration of the essential functions of these hormones. So it is with the tendency of steroids to produce tissue fluid accumulation or 'oedema',  most commonly seen as swollen ankles.

General effects

Steroids can produce feelings of well-being sometimes approaching euphoria with, in some people, a strange 'low' feeling afterwards. Very rarely they can produce mental confusion.  All of this simply reflects the actions of natural steroids in excess. Some patients complain of an inability to sleep when on high dose steroids. The best way to avoid this problem is to take steroids in the morning when the body expects a higher level, rather than in the evening, when they would be naturally low.

Other Side-effects

In the presence of high levels of steroids the skin is thinned, making it more fragile with a tendency to bruise easily. Where this thinned skin is stretched over the increasing abdominal fat pink stretch marks may be produced. The skin also becomes more greasy with a tendency to acne. If corticosteroids are given in high doses for several years they adversely affect the skeleton, leading to thinning of bones, known as osteoporosis. Apart from the acne, these long-term steroid side-effects are extremely uncommon in the regimes used to treat lymphomas.

Finally, high dose steroids reduce the body’s ability to fight infection. In particular, patients become prone to viral infections, such as cold sores, shingles, and fungal infections, especially thrush ('candida').

What steroid side-effects might a patient being treated for lymphoma expect from a typical chemotherapy regime in which high dose steroids are given off and on at quite high doses for several months? Most prominent is the weight gain, particularly around the face and  accompanied by an increased appetite. Abdominal stretch marks are uncommon. Fluid retention may cause ankle swelling which is rarely troublesome. You could develop oral thrush with a sore mouth, though this is easily treated.  You may notice a tendency to spots and cold sores. Older patients may find that their skin is more fragile with a tendency to bruise relatively easily. Women may be troubled by vaginal thrush, again, straightforward to remedy. During the steroid treatment days you may feel less tired, with more energy but experience sleep disturbance especially if the steroids are taken late in the day. Most regimes do not cause long-term adrenal gland suppression and it would be exceptional if they caused sufficient bone problems to cause symptoms.

So far you have seen what steroids are, what they do in nature and what side effects you can expect from the similar artificial manufactured durgs, and why. You may, by now, be asking yourself the question. "Why on earth do we use these drugs if they can cause so many problems?" In the case of lymphoma treatment the simple answer is because they work! The Lymphoma Trials Office (LTO) and others have done many clinical trials to prove it.

It seems that high levels of steroids are very toxic to lymphocytes, the blood cells which give rise to lymphomas. This is one of the reasons why steroids suppress the immune system, of which lymphocytes are a crucial part. Quite how steroids kill lymphocytes and inhibit the growth of lymphomas is still a subject of intense research and the explanations are likely to be complex indeed. Effective treatments often become established years before their success is ever explained.

Steroids came into use in the treatment of lymphomas and leukaemias long before most of the established chemotherapy drugs. In the 1940’s they were found to cause shrinkage of lymphoma-like tumours in rats and so were very soon put to use in these conditions in humans, which were largely untreatable at the time. However, used alone, steroids cause only temporary and partial reversal of most lymphomas. When they are combined with cytotoxic chemotherapy drugs this regression can be prolonged and in many cases complete and permanent.

Although steroids are now an essential part of most chemotherapy regimes for both Hodgkin lymphoma and non Hodgkin lymphoma, they have also been used in cancer medicine generally. Dexamethasone, for example, is a highly effective anti-sickness drug and is often used with many different chemotherapy regimes for all sorts of cancers. Steroids are also important drugs in advanced cancer where a cure is no longer possible and symptom control is the priority. They can be used to improve the appetite of a patient who is rapidly losing weight. They can also improve the patient’s feeling of well-being and energy levels, as well as reducing painful tissue swelling or pressure caused by a variety of cancers. All of these benefits can be obtained with quite modest doses and without significant side effects.

Key points