The Pill, often known as the oral contraceptive pill or the birth control pill, is not just one drug but rather a group of many drugs first developed for use as a contraceptive in the late 1950s. Initially, they were made up of a combination of synthetic oestrogen and progestogen (synthetic progesterone) but since the 1970s various synthetic progestogen-only drugs have also been used.

The Pill was first used as a treatment for endometriosis in the late 1950s and for many years it was the main form of treatment. It has now been superseded by Danazol and the progestogen-only drugs such as Duphaston and Provera.

Nowadays, many gynaecologists believe that there is no place for the Pill in the treatment of endometriosis because they feel it does not effectively eradicate the condition. However, many gynaecologists believe that it still has a role in the long-term management of endometriosis because they feel that although it does not eradicate the disease it may slow down or halt its progression. Therefore it is sometimes recommended for women with mild or minimal endometriosis in an attempt to stop the progression of their disease.

How the Pill works

It is thought that the Pill works by mimicking the hormonal condition of pregnancy because it leads to high levels of oestrogen and progesterone in the body. The high levels of oestrogen and progesterone suppress ovulation and lead to changes in the endometrial implants which eventually cause them to waste away.

Sometimes the Pill causes an initial enlargement and softening of the endometrial implants and cysts in the first few weeks or months of treatment, which may result in a worsening of symptoms and may occasionally cause endometriomas to rupture.

Dosages of the Pill generally used

There are many different varieties of the Pill available but not all of them are used for endometriosis. Initially, various high dose combinations were used but nowadays most gynaecologists would recommend a combination with a low dose of oestrogen and a relatively high dose of progesterone. The progesterone-only

Mini-Pills are not suitable.

Regardless of the combination used, most gynaecologists recommend that the Pill be taken continuously — every day without a break, for six to twelve months. You will usually be advised to begin with one tablet per day and to increase the dosage by one tablet per day if any vaginal bleeding occurs. The final dosage will usually be the lowest dosage on which you have no vaginal bleeding and this may be three or four tablets per day.

Side effects of the Pill

Side effects when using the Pill for endometriosis are common. Many women experience a greater number of side effects and they are often more severe than those experienced when using the Pill as a contraceptive, because the dosages used for endometriosis are usually much greater.

The more common side effects include vaginal bleeding, fluid retention, abdominal bloating, weight gain, increased appetite, nausea, headaches, breast tenderness, acne, depression, changed libido and vaginal thrush.

You will usually begin to ovulate and menstruate again within four to eight weeks of ceasing treatment and any side effects usually disappear within a few weeks.

How effective is the Pill

As previously mentioned, most gynaecologists these days do not believe that the Pill is an effective treatment for endometriosis. The research suggests that only a small proportion of women obtain relief from their symptoms and that the likelihood of becoming pregnant following treatment is low. In addition, the likelihood of developing a recurrence of the disease soon after treatment is high.

The Pill, pregnancy and breastfeeding

The Pill should not be used during pregnancy as progestogens can cause abnormalities in the developing foetus.

The use of the brands of the Pill containing both synthetic oestrogen and progesterone while breastfeeding is not recommended. The progestogen-only Mini-Pills may be safely used while breastfeeding.

Interaction with other drugs

The Pill interacts with a number of drugs therefore you should tell your gynaecologist if you are taking any other medication.

*59\83\2*

The Flower Remedies were created during the 1930s by Dr Edward Bach, a noted homoeopathic physician and bacteriologist, to treat ‘emotional imbalances’. Although originally formulated primarily to supplement homoeopathic preparations, the remedies have since been used for all kinds of health problems. Similar to the Flower Remedies – of which there are 38 different varieties, all created by Dr Bach – are the Flower Essences which were developed later by followers of Dr Bach.

Much of the evidence about the efficacy of these remedies is anecdotal, but many people with back problems have reported that their symptoms were eased by the formulations. While the remedies are available without prescription in many health shops and pharmacies, it is no easy matter to select the right one, and it is therefore best to first consult a qualified practitioner.

*63\124\2*

Many of the suggestions of A. Cornelius Celsus mentioned above are healthy pleasures – music, soothing sounds like that of running water, cheerful conversations, massage and travel. Whatever it is that is a source of pleasure should be sought out and developed by the depressed person because the essence of depression is the lack of capacity for enjoyment, also known as anhedonia. But even when a certain degree of anhedonia is present, some activities might still provide pleasure.

Pets, for example, can be a great source of comfort and delight even to depressed people. Many years ago I decided that it would be a useful exercise to put several of my depressed patients together in a group. I reasoned that they might be able to help one another cope with depression. In truth it was not a good idea. The group was suffused by a sense of communal gloom and despair. But I remember on one occasion when someone mentioned her dog or cat, there was an immediate change in atmosphere as each of the group members pulled out a picture of his or her pet – animals that until that moment I had not even known to exist. For some time they pored over one another’s photos, admiring the animals and discussing their various special qualities and foibles. It was a vivid demonstration to me of the power of animals to cheer people up and how even depressed people are capable of spells of happiness if they are presented with the right stimuli.

Only you know what it is that delights you most when you are feeling well and how best to seek such activities out. Ask yourself what it is that still appeals even though you may be depressed. Is it painting watercolours, growing orchids or taking long walks in the countryside? The possibilities are limited only by the imagination. Consider the question, make a list of such sources of joy and then devise strategies for how you can bring them back into your life again.

I specify healthy pleasures because some pleasures are quite unhealthy, even if they are capable of bringing you out of depression for brief periods. Such pleasures may include alcohol and addictive drugs and compulsive behaviours, such as excessive shopping, spending, gambling or sexual activity. One of my patients, for example, would regularly go and shop for clothes that she could ill afford, did not need and in fact hardly ever wore. Her cupboards were full of expensive dresses that she had never even tried on after leaving the shop. For her, all the reward came from the act of shopping itself. There was something about the process of going to an expensive shop, trying on the garment, and having the saleslady pay attention to her and compliment her that proved irresistible. Of course, the comfort was very short-lived and the cost of the habit, both financially and in the form of marital conflict, severely exacerbated her depression. There are many different varieties of this habit and they can be very difficult to break. Addictive sexual behaviour is another costly way that some people use to medicate their depressed feelings. At times I have recommended specific recovery groups for these types of problems, with fairly good results.

And how do you tell the difference between a healthy pleasure and an unhealthy one? Usually it is fairly obvious. The one leaves you feeling good afterwards; the other leaves you feeling bad. The one feels like a wise investment that continues to yield dividends over time; the other like a foolish expenditure of time, money and energy, which ends up costing more than it’s worth. And finally, the one is a source of pride that you might be pleased to share with friends and family, whereas the other is often a source of shame, cloaked in secrecy.

*78\75\2*

Until about 40 years ago most doctors believed that inheritance was a major factor in causing epilepsy. This belief is still strong amongst the population at large. Doctors are often told ‘It can’t be epilepsy because there is nothing like that in the family,. These views were held in the past with such force in some states of America and in some Scandinavian countries that it was illegal for people with epilepsy to marry. It is certainly true that genetic factors do play a part in epilepsy, but not an overwhelming part.

There are some genetic diseases in which inheritance is through a dominant gene. Genes come in pairs, one from each parent. One member of the pair may always be dominant in influencing the structure or biochemistry of the offspring. If a child or adult has the gene, then, in broad terms he or she has the disease, although there are variations in the severity of the disease. One of the parents; carrying the gene will therefore not only show the effects of the gene himself or herself, but will transmit the effective gene to, on average, half his or her children. Tuberous sclerosis and neurofibromatosis, both disorders affecting the structure of nerve cells and surrounding tissue, are transmitted in this way.

There are other genetic diseases in which the gene is recessive. In recessive inheritance, the effects of the gene are only expressed if a child has a double dose of the relevant gene—one abnormal gene from each parent. The parents, although themselves carriers, do not show the abnormality as the other member of their pair of genes is normal. There are certain rare disorders of metabolism of the brain, collectively known as the lipidoses, which are inherited by recessive genes. Fatty substances known as lipids are important constituents of the membranes surrounding the nerve cells. A disorder of the structure and function of the cell membrane may well lead to paroxysmal discharge of nerve cells—an epileptic seizure.

It must be stressed that these diseases are rare. They have been mentioned first only because the mechanism of their inheritance is most clearly understood.

There is, however, also good evidence that primary generalized idiopathic epilepsy is also inherited. In order to explain this, it is easier to trace back from a child with epilepsy to his parents, rather than first considering the chances of a prospective parent with epilepsy having an epileptic child. The characteristic EEG is seen in about 40 per cent of brothers and sisters of children with primary generalized epilepsy, even if these brothers and sisters have not had any apparent seizures. That is to say, the abnormality which causes the abnormal EEG record is inherited, but this abnormality is not necessarily expressed in clinically apparent seizures. A smaller proportion of the parents of children with primary generalized epilepsy will also show the characteristic EEG changes. We know from following the children with these EEG changes that the characteristic discharges become much less frequent with age, so the absence of discharge in adult life does not mean that the parent did not have unrecorded and unapparent discharges in childhood. From mathematical studies of the proportion of the abnormal EEG records of many families with primary generalized epilepsy, it is possible to calculate that the pattern of inheritance is probably that of a dominant gene.

Energetic research studies are ongoing in several centres to identify the gene. It will probably turn out that there is more than one gene, each giving a similar clinical picture. This has already been shown to be true for the much more clearly defined disorder of tuberouss sclerosis, a disorder in which there are nests of abnormally developed nerve cells and their supporting cells (known as glial cells), some of them calcified and some sufficiently large to be seen on a brain scan. It is now known that two dominant genes on separate chromosomes can result in what appears to be an identical picture. (A chromosome is the microscopically visible structure within the nucleus of a cell which contains the genetic material—the DNA.)

As we have already explained, for a child to show an abnormality in cases of dominant inheritance, only one member of the pair of relevant genes (one from the father and one from the mother) needs to be abnormal. However, the effects of other gene pairs may to some extent succeed in suppressing this gene from expressing itself in obvious seizures. This means that about only one third of the children to whom it is transmitted will have seizures. Furthermore, even if the gene is expressed in seizures, the result may only be a few absence seizures in childhood.

The variability in clinical expression of the genetic abnormality accounts for the occurrence of primary generalized epilepsy in a child of parents neither of whom has ever had a known seizure. In such an instance one assumes that one parent does indeed have the gene, and, had an EEG been recorded in his or her childhood, the typical EEG discharge would have been seen.

Another aspect is the inheritance of a convulsive threshold. Any one of us can be made to have a seizure ii the stimulus is strong enough, and some of us do at lower levels of stimulus—at lower thresholds—than others. The inheritance of this level of threshold is probably

polygenic—that is to say, several genes, some recessive and some dominant, interact to produce the final result. Another example of polygenic inheritance is height. Tall parents tend to have tall children, but height is not determined by a single gene.

This inherited convulsive threshold is a background, as it were, to the whole of the area. It influences even those cases in which epilepsy clearly seems to be secondary to some obvious cause, such as a severe head injury causing local cortical scarring. Head injuries obviously are not inherited as such. Nevertheless there is a slight tendency for those who develop epilepsy after head injury to have a family history of epilepsy more often than those who do not develop epilepsy after what may be regarded as a comparable injury. What is being inherited here, through a number of different genes, is a lower-than-average convulsive threshold. The children of such head-injured parents are not likely to have seizures unless some additional cerebral damage affects them. It would be an unlikely family in which two members suffered severe head injuries, so that the risk of ‘inheriting’ epilepsy from a parent with epilepsy secondary to some structural brain damage is small. It follows that one good reason for a paediatrician or neurologist to do his or her best to find a ’cause’ for epilepsy is so that they can best advise about the risk of brothers or sisters or daughters or sons being affected.

There is, however, one group of people in whom inherited and acquired characteristics interplay in a complex way. The tendency to febrile convulsions is inherited, through one or more genes.

A febrile convulsion, if very prolonged (lasting longer than 20-30 minutes), may rarely damage one or other temporal lobes of the brain through lack of oxygen occurring during the seizure. The scar in the temporal lobe may then act as a focus from which paroxysmal discharge—seizures—spread in later childhood and adult life.

The first duty of a doctor asked by a young couple, one of whom has epilepsy, about the chances of any child of theirs having epilepsy, is to characterize the seizure type as accurately as possible, using the description of the seizures and the EEC if it is clear that the prospective parent is having partial seizures, of generalized seizures which have a clear focal onset, either clinically or demonstrated on the EEG then, these seizures are almost certainly secondary to some area of cortical scarring or developmental abnormalities. The risk of any child of this marriage having epilepsy is only moderately higher than the risk of the population at large. It is, however, somewhat higher than the risk of the average child because of the inheritance of the convulsive threshold. If it is clear that the prospective parent has primary generalized epilepsy, then we have to say that about half his or her children will carry the gene, but only about one child in six will have definite seizures. The chances of epilepsy being a significant problem in the life of a child of a parent with primary generalized epilepsy is no more than of the order of five per cent, the others perhaps having only a minor EEG abnormality if that is specifically looked for.

A small fraction of the genetic material (DNA) is carried outside the nucleus in small particles in the cell known as mitochondria. These are only derived from the maternal ovum, not being present in sperm. There are therefore a few rare disorders in which inheritance is only through the maternal line. Some of these are associated with epilepsy.

*17\188\2*

Symptoms: blisters containing thin, yellow pus; broken blisters developing into open, weeping sores; pus dries to consistency of hardened honey.

Home care

A mild case of impetigo can be treated by scrubbing the crusts of the sores with soap and water, then applying a nonprescription antibiotic ointment at intervals.

Cover the affected area with gauze; this will help keep the child from scratching and spreading the condition.

Precaution:

-    Impetigo is highly contagious (catching).

-    Minor scratches and scrapes on the skin may invite impetigo; to avoid infection, clean such minor wounds with soap and water and cover them with a sterile bandage.

-    Keep an infected child’s clothes and from those used by members; this will help disease from spreading.

    Launder the child’s clothes frequently.

-    If home treatment for impetigo is effective, continue it until all the sores are completely healed; it can take a long time to eliminate the condition.

-    See the doctor if home treatment is not effective.

Impetigo is a highly contagious infection of the outer layers of the skin. It’s caused by staphylococcus and/or streptococcus bacteria. The germs are transmitted by direct contact when the child touches either an infected person or something that person has been using – for example, clothing, towels, or toys. The condition appears two to five days after the child has been exposed to the germs.

*124/84/5*

How to tell if breathing has stopped

1. Put your cheek against the person’s mouth and feel for breaths.

2. If breathing is not obvious, purse the person’s lips and try your cheek again.

3. Look for chest movements (though these may be difficult to see because of bulky clothes).

If breathing has stopped

1. Lay the person on the ground.

2. See if there is anything in the mouth (vomit, false teeth, foreign body, etc.) that might be causing obstruction. If so, remove it and lay him or her on his or her back. Kneel on the ground on his or her left side.

3. Pull the chin upwards so that the person’s neck is bent backwards. With your left hand pulling the chin up, push the top of the head down with your right. This simple procedure opens the airway at the back of the throat and may re-start breathing. If it does, put the person into the recovery position and stay with him or her.

If breathing does not re-start at once Start artificial respiration while someone else gets a doctor or an ambulance. The best method by far of re-starting breathing is the ‘kiss of life’ (mouth-to-mouth resuscitation).

1. Put the person on his or her back.

2. Tilt head back as far as possible (nostrils then point directly upwards at you), using both hands together.

3. Cup one hand under the chin.

4. Put the heel of the other hand on his or her forehead so that the fingers of that hand can pinch the nose.

5. Pinch the nose shut.

6. Make sure the mouth is open.

7. Take a full breath yourself.

8. Apply your mouth to the person’s, ensuring that there is a good seal all round.

9. Breathe into the open mouth firmly and slowly-don’t puff out hard. As you do this, the person’s chest will rise.

10. Take your mouth away, breathe in fully while the air escapes from the person and repeat the procedure.

11. While you are taking a breath in, the person will breathe out spontaneously.

12. Repeat the breathing into his or her mouth and watch for spontaneous re-starting of breathing as you turn your head away to breathe in yourself.

13. Try to ‘blow’ a breath into the victim about every six seconds. Be guided by common sense on this. For example, the first few breaths can be given much more quickly to get some oxygen into the individual.

14. Stop when the person shows clear signs of re-starting to breathe, but even then keep a close eye on his or her chest movements until professional help arrives.

Some useful hints

1. Don’t blow too hard as this may send air into the stomach and make the person vomit, which is dangerous for him or her and unpleasant for you.

2. Should vomiting occur, turn the person’s head to one side and let the vomit dribble out of the mouth. Clean out the mouth and carry on with resuscitation.

3. If a child is the victim, seal your lips over both nose and mouth after positioning the head as before. Only blow gently. Be guided by what produces a rise and fall of the chest wall. In babies, use only the amount of air you can hold in your cheeks-don’t blow from your lungs.

4. If the abdomen starts to swell up, you will know you are blowing air down the gullet into the stomach instead of down the windpipe. Stop resuscitation for a moment, turn the child to one side and press firmly over the swollen stomach. This will probably force the air out.

5. Check that the person’s heartbeat has not stopped by feeling in the neck beside the Adam’s apple for the carotid pulse from time to time.

How long to continue

Either:

Until the person starts to breathe easily again. Never try breathing into someone who is already breathing spontaneously. It can be helpful, though, to give the odd helping breath if he or she is gasping or breathing irregularly.

Or:

Until professional help arrives. This may take time, so get others to help you. Keep going until a doctor says the person is dead. Don’t give up too readily, especially in cases of drowning. People have been revived after an hour of resuscitation. Once breathing re-starts try not to let the victim die of hypothermia. Remove wet clothing, and wrap him or her in blankets or a sleeping bag. Never give alcohol (which will increase heat loss).

*142/72/5*

Carrying out the trial

At this point our patients should have lost the effect of most drug therapies which they had been on and should be in a fairly suitable condition for the trial. Use of pain-killers will be helping somewhat with aggravated conditions that have arisen through lack of treatment. The reason for specifying that the pain-killers should not be of the aspirin type is that this type is also effective as an anti-arthritic treatment and would influence our results.

Our thirty patients are divided at random into two groups of fifteen and are administered either placebo or active substance over a period of eight weeks. Weekly checks on the condition of each patient are made and recorded. At the end of eight weeks we reverse the treatments, so that those who had been receiving placebo would now be treated with the active substance, and vice versa. Of course, no one other than the holder of the code knows which is which. Weekly conditions of each patient are recorded for the next eight weeks and the trial then ceases. We now have to analyze the data collected and compare active and placebo results for each patient. This is where the weakness of this trial will show up.

Assessing the results

As we are conducting an imaginary trial we will not have any actual results. It will therefore be necessary to look at the trial critically and see what sort of results we could get from it.

Take the case of imaginary patient ‘A’ who, after the three weeks run-down period to clear the system of any previous drug therapy, happens to receive the placebo treatment first.

This patient receives no treatment at all (the pain-killers are not treatment for the disease) for the period of eleven weeks. By this time the patient’s condition has deteriorated to a considerable degree. Now the active substance is given. Suppose that it is effective for this person, and that it begins to rectify the situation. It will probably take the whole eight weeks to bring the patient back towards the condition he or she was in at the start of the trial. Remember, we have at least fifteen patients who will have been treated with placebo first and whose circumstances may well be very similar. If we now do what is required by this trial process, that is, measure the difference between patient condition on active treatment and on placebo, we will find in all probability that there is no significant difference.

Now let us take the case of patient ‘B’, who is also representative of fourteen other patients. This person, after the three weeks of no treatment, begins the trial on the active substance. Again, let us assume that the substance works for our patient and an improvement in condition begins to take place about six weeks from starting the trial. This is looking good: how can we fail with this one? Unfortunately we can, because at eight weeks from the start of the trial we change the patient to placebo. Because our active substance is effective for a long time it continues to maintain the patient in good condition throughout the eight weeks of placebo treatment. Now we come to study our results and find that in this case the patient seemed to do as well, if not better with placebo as with the active substance! Thus, the conclusion must be drawn that the trial has demonstrated no significant difference in the therapeutic effect of the active substance compared with placebo.

Quite so: this is precisely what the trial has demonstrated, but it is not ‘Seapower’, our active substance, that has failed: it is the trial procedure itself.

It is possible to select suitable procedures for trials of substances like our imaginary one. It is also important that the people responsible for setting up such trials do select appropriate procedures. The very reason that this subject has been emphasized so strongly here is that personal experience has shown that this is not always done. The ones who lose out through such negligence are the people awaiting effective new treatments.

Some doctors are now advocating changes in the trials system to take account of failures like the one just described. Not only are better trial designs being suggested, but also shorter periods of involvement are being recommended. Whilst the need for thorough testing of new substances is appreciated, the lengths to which some of the governmental agencies go, possibly in the interests of self-protection, are becoming ridiculous. The banning of saccharin by the United States Food and Drug Administration on the grounds that it is cancer-producing demonstrates this trend. Many things are, or can be shown to be, dangerous if used to excess but are quite safe in normal use. The sun is carcinogenic (cancer-producing): let us hope they do not ban that! It is probable that many of the more practically-minded scientists involved with trial techniques for the safety, and efficacy of materials realize the negative effect that results from some of our present systems and will effect a change for the better.

*30/48/5*

Although breast reconstruction is normally done after a mastectomy, it can be worthwhile for women with significant distortion or asymmetry of the breast following a segmentectomy or lumpectomy. Surgical reconstruction of the breast is an option being taken up by increasing numbers of women.

Each of the many possible techniques for breast reconstruction has its own merits and disadvantages, and any one of several may be suitable for a particular woman. However, what is most appropriate for one woman may not be appropriate for another, and it is important that before undergoing any type of breast reconstruction, you discuss your options with your reconstructive surgeon so that, between you, you can choose the most suitable one.

Breast reconstruction can involve using only the woman’s tissues, imported to the chest from another part of her body, or implanting an artificial prosthesis with or without the use of the woman’s own tissues.

Prosthetic reconstruction

Reconstruction of the breast with a prosthesis, or implant, can usually be done immediately after a mastectomy, thus making use of the existing mastectomy incision, and requiring very little additional operative time. However, reconstructing a breast to match a normal ‘droopy’ breast is difficult with prosthesis alone.

The prosthesis itself consists of a silicone envelope which can be filled with various liquids or gels to mimic the consistency of normal breast tissue beneath the skin.

The recent controversy about the long-term safety of silicone gel as a filling for breast implants has led to the current restrictions on its use in the USA. The Health Department in the UK does not consider there is sufficient evidence to warrant such restrictions, and therefore this type of prosthesis is still widely used in the UK. You should discuss with your reconstructive surgeon the advantages and disadvantages of each of the different fluid fillings before you make a decision.

If there is not enough skin remaining on your chest after a mastectomy to allow the simple placement of a prosthesis beneath it, skin may have to be imported from another part of the body, usually the back or upper abdomen, to create a space for the prosthesis.

Tissue expansion

A possible alternative to importing skin is to expand the existing skin of the chest by inserting a special balloon beneath it, which is then gradually inflated with a salt solution over a period of weeks or months until the correct size of breast is achieved. Once the skin has been stretched sufficiently, the balloon can be removed and replaced by a soft, permanent prosthesis. To recreate the natural droop (ptosis) of the breast, the skin is over-expanded before the implant is inserted.

There are several special ’tissue expanders’ which can be used which already contain the permanent prosthesis and which do not therefore need to be removed once expansion of the skin is completed, although a minor surgical procedure may be necessary to remove the filling valve.

For women whose pectoralis major muscle is still intact, the tissue expanders can be placed in a pocket underneath this muscle rather than directly under the skin. This helps to reduce the risk of complications occurring in the future, particularly for women who have had radiotherapy, which damages the blood vessels in the skin, and may weaken it and make it more likely to allow protrusion of a breast prosthesis.

Although good cosmetic results can be obtained by tissue expansion, and an artificial nipple can be created with a skin graft, it should be understood that, as with all methods of reconstruction, a perfect breast cannot be refashioned in this way.

Side-effects of prosthetic reconstruction

If an infection develops following prosthetic reconstruction, the implant may have to be removed, at least temporarily. Protrusion of the implant may occur if the skin has been weakened for any reason, e.g. by radiotherapy or an infection.

Although the body generally tolerates the foreign material of a prosthesis, a capsule of fibrous tissue forms around it as the body walls it off. In some women, the fibrous tissue becomes thick, and the capsule it has formed around the implant contracts, thus altering the shape of the prosthesis and causing a marked firming in the texture of the reconstructed breast. When this complication – known as capsular contracture – does occur, it is most likely to do so within the first year or two after the implant has been inserted, although it is possible many years later. The breast may become hard and painful, and sometimes further surgery is necessary to regain the desired breast shape or to remove the implant.

Other possible complications of prosthetic reconstruction include the implant moving from its original position, or leaking or deflating. Surgery may be necessary in these cases to reposition or replace the prosthesis.

*57/39/5*

Provera is one of the hormonal drugs that is used to treat women with endometriosis. In the past, Provera was used infrequently in Australia for the treatment of endometriosis but its use has increased markedly over the last four or five years. It has also been used for over 25 years to treat a number of other conditions including endometrial cancer (cancer of the uterus), abnormal uterine bleeding, amenorrhea (absence of periods) and menopausal symptoms in some women.

Provera is a strong progestogen (a synthetic progesterone) which is sometimes also known by its chemical name, medroxyprogesterone acetate.

Provera tablets, manufactured by Upjohn, come in several strengths. Those most commonly used in the treatment of endometriosis are small, white 10 milligram tablets.

Provera should not be confused with its controversial close relative Depo-Provera. Although both have the same chemical composition, Provera is in the form of a short-acting tablet whereas Depo-Provera is in the form of a long-acting injection. The long-term side effects that may be associated with the use of Depo-Provera do not occur with the use of Provera. If side effects occur when using Provera they can be rapidly reversed by stopping the treatment because the drug does not remain in the body for a significant length of time. The delay in the return of ovulation that sometimes occurs following the use of Depo-Provera is not a problem with Provera.

How Provera works

It is not known precisely how Provera eradicates endometrial implants but it probably works by suppressing ovulation and inhibiting the growth of the misplaced endometrial cells in some way, causing them to gradually waste away.

At the dosages usually recommended for endometriosis most women will stop ovulating and menstruating.

Dosages of Provera generally used

Most gynecologists recommend dosages of Provera in the range of 20 to 60 milligrams a day (two to six 10 milligram tablets a day). Generally, gynecologists recommend that Provera be taken daily for three to nine months.

Although the usual length of treatment is three to nine months there is no evidence that prolonged or repeated courses of Provera cause long-term side effects.

You should visit your gynecologist about six to eight weeks after starting your course of Provera so that you can discuss how me treatment is progressing. Thereafter, you should visit every two to three months for the remainder of your course of treatment.

Side effects of Provera

Most women using Provera will experience one or more side effects which are usually mild to moderate in severity and generally quite manageable. A few women will find them intolerable.

The more common side effects are weight gain, bloating, spotting, irregular vaginal bleeding, decreased libido, lethargy and tiredness, depression, headaches, acne, nausea and tender breasts.

The amount of weight gain on Provera varies widely and although most women will gain only one or two kilograms some women will experience greater gains.

Vaginal bleeding is a significant problem for some women on Provera. Usually it can be controlled by increasing the dosage but some women will continue to suffer vaginal bleeding even if they take relatively high dosages in the order of 60 to 80 milligrams per day.

Ovulation and menstruation usually occur within four to six weeks of completing therapy.

The side effects of Provera are reversible and they usually disappear within a few weeks of completing treatment.

There are no known long-term side effects of Provera.

How effective is Provera

Although very little research has been carried out into the effectiveness of Provera the results so far indicate that it is as effective as Danazol.

Studies have shown that about 60% to 80% of women had partial or complete relief from their symptoms and that about 50% of the women who wished to conceive became pregnant following treatment. There is no information available on how frequently endometriosis recurs following treatment.

Provera, pregnancy and breastfeeding

The manufacturers of Provera state that it should not be used during pregnancy as progestogens may cause abnormalities in the developing foetus.

The use of Provera while breastfeeding is also not recommended by the manufacturers. Small amounts of progestogens have been found in the milk of mothers taking them and the effect on the child is not known. However, some gynecologists believe that Provera can be safely used during pregnancy and breastfeeding.

Interaction with other drugs, alcohol or foods

There are no known interactions of Provera with any foods, alcohol or other drugs.

*40/41/5*

Fenfluramine: This product also enhances serotonin activity and is widely used to promote weight loss in obese people. Recently a study found that fenfluramine may significantly reduce symptoms of both bulimia and depression.

Opiate antagonists: Certain drugs can block these endogenous opiates and thus reduce their effect on behavior. One of these products, naltrexone, is used to treat heroin addicts. Theory has it that naltrexone may also have a role in managing eating disorders. However, clinical results so far are mixed. One study turned up no evidence that naltrexone led to weight loss in obese people. And a study at the usual dosage level failed to show any impact on bingeing behavior, although a study at a dosage four times as high saw a significant reduction in bulimic symptoms. Unfortunately, such high doses also resulted in a high rate of nausea and a serious risk of liver toxicity.

Anticonvulsant drugs: In some ways, bulimia resembles a seizure disorder such as epilepsy. Seizure disorders involve misfires in the electrical system of the brain. Like seizures, bulimic binges are episodic – that is, they occur at unpredictable intervals rather than constantly. Both binges and seizures make their victims feel out of control. Many bulimics look on their binges as repugnant or inconsistent with their true personality-in other words, they feel their binges are somehow foreign, not really a part of themselves. People with seizures often make similar remarks.

To find out whether eating binges were the result of faulty brain wiring, some researchers studied the electroencephalograph readings of bulimic patients. Because they found brain waves similar to those seen in epilepsy, these researchers tried giving their patients phenytoin, an anti-seizure medication (sold under the brand name Dilantin). They reported that the drug was effective. Unfortunately, subsequent studies, failing to replicate these findings, indicated no more than mild results with phenytoin.

Another study looked at carbamazepine (sold under the brand name Tegretol), an anticonvulsant related to the TCAs that is used to treat seizure disorders and manic depression. Results showed that carbamazepine had a profound effect on a bulimic woman who also suffered from a mood disorder that resembled manic depression, but had no effect on five other patients in the study.

Thus the notion that bulimia is primarily a form of seizure disorder, and that anti-seizure medications can help, hasn’t won many supporters over the last twenty years or so.

Anti-anxiety medications: Anxiety can set the binge-purge cycle in motion. Because therapy must address the patient’s anxiety, naturally it’s tempting to consider using one of the many anti-anxiety drugs on the market.

Perhaps the most widely known of these are the benzodiazepines such as diazepam (sold under the brand name Valium). We used to call these “minor tranquilizers” because they seemed relatively safe compared to the “major tranquilizers,” such as chlorpromazine.

We now realize there’s nothing “minor” about them. These powerful medications have a high potential for abuse and can lead to dependency. In the state of New York, for example, the law now requires that doctors follow the same procedures in prescribing benzodiazepines as they do when prescribing narcotics, another class of drugs with high potential for abuse. As we have seen, bulimics have a high incidence of substance abuse, and may misuse an anti-anxiety drug. Side effects include drowsiness, disorientation, and headaches.

Anti-anxiety medicines do have a specific use, however. I may prescribe them for a limited time when a patient knows she is about to face a highly stressful situation, such as a family reunion or a trip home for Thanksgiving.

Stimulant medications: Although amphetamines may help reduce appetite and produce antidepressant effects, these drugs have a high potential for abuse and are almost never appropriate for use by bulimics.

Lithium carbonate: Some physicians have given lithium, commonly used in treating bipolar disorders, to bulimics. A few of those treated, including some who didn’t respond to other antidepressants, noticed a drop in their bingeing and purging episodes. We don’t yet have good controlled studies proving the effectiveness of this medication. Lithium has a serious drawback: It depletes the body’s supply of potassium. As we have seen, bulimics who vomit a lot or who abuse laxatives or diuretics are already at risk of low potassium. The medical literature contains at least one report of a bulimic woman who died of cardiac failure caused by the combined effects of vomiting and lithium.

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