Discard for protection

2008/09/01 Lakar Iraizoz, Oihane - Elhuyar Zientzia Iturria: Elhuyar aldizkaria

• Anatomia/Fisiologia
• Farmakologia
• Medikuntza

(Photo: From archive)

Women are physiologically more variable than men. Because of the sex hormones, women suffer cyclic alterations that men do not have, among other things, in a age group increase and lower the hormones every month, become pregnant, sometimes adopt hormonal contraceptives to avoid pregnancy and stop producing sex hormones from a certain age.

All these processes can alter the effect of the body on drugs. For example, hormonal contraceptives can alter the absorption of certain drugs, such as psycho-drugs, and some enzymes that are responsible for metabolizing drugs in the liver have a greater or lesser activity due to sex hormones. Therefore, for the effect to be the same in men and women, one should take more doses of one drug and a smaller one.

From the point of view of a clinical trial, the need to take into account all these incidents of women could make the experiment more difficult and expensive. Clinical trials are the last experimental phase that is performed before the exit of a drug. The researchers deliver the medicine object of study to several people to check their response to this drug. Depending on these responses, they determine the doses to be taken, the possible side effects of the medication, etc.

When designing a clinical trial, the researchers try to have the smallest number of possible variables involved in the experiment. The fewer variables there are, the more easily they can relate the reactions they observe with the effect of the drug.

Based on this criterion, and in view of the variability of women, researchers have had a great tendency to use exclusively men in clinical trials for a long time. They saw nothing wrong with it, because they were convinced that the differences between men and women were limited to sexual organs. Therefore, they considered it much more comfortable, simple and effective to use volunteers who had no fluctuations in time, for the benefit of the trial.

Protection of children

Birth control hormones can alter the absorption of certain drugs, such as psycho-drugs.

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Gradually, certain drugs caused serious side effects in pregnant women. The case of the talidomide compound was very famous: It was published in 1958 to treat insomnia and anxiety. It was also done by pregnant women to deal with the discomfort caused by pregnancy. They did not know that this substance caused malformations in the fetus and thousands of malformed children were born.

Faced with this, women went from being unnecessary in the trials to being the object of protection and total exclusion of the trials. It was necessary to protect its fertility. The response was total by the authorities. For example, in 1977, the U.S. Food and Drug Regulation Agency (FDA) clearly stated that reproductive women were prohibited from participating in clinical trials.

However, they did not realize that this decision, which was intended to protect, not only harmed women. These same reasons that led women to exclusion serve to verify that they need to be taken into account in clinical trials.

To take a drug, it would be necessary to know if men and women respond in the same way to a specific treatment, if the effect of the drugs varies with the monthly cycle or after menopause, if the treatments of artificial hormones (both contraceptives and those used to deal with the symptoms of menopause) have some influence and if the drug affects both pregnant women and children.

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The tendency to exclude women from clinical trials means that much of the scientific knowledge we currently have is not complete.

From file

This tendency to the exclusion of women from clinical trials means that much of the scientific knowledge we currently have is not complete. With the passage of time, health organizations realized a great mistake and began to recommend the participation of women in clinical trials. The above-mentioned FDA ban was in force until 1993. It was then when it began to be said that women had to be included in the trials and, once the trial ended, differentiate the consequences by sex.

It is not the same to include women in clinical trials to analyze the results obtained in the trial by sex. If women have been included in a specific research, but in the interpretation of the results, men and women have not been analyzed separately, the incidence of drugs in one and the other appears mixed. And it is possible that the effect, side effects, and other effects are different in both.

In Europe, for about fifteen years it has been beginning to raise awareness of the importance of women, who are increasingly valued. The laws are changing little by little, they have begun to give recommendations, but they still do not say anything concrete, they remain in general. They say that women's participation should be proportional to the impact of the disease studied in the population and that women should be properly represented.

However, they do not specify how clinical trials should be designed or how the ethics committees that analyze the clinical trial projects in this field should act, or how they should be presented once the clinical trial has been conducted.

how sex information should appear in the reports. These reports are the only information available in clinical trials. In them, the results of the research carried out are collected. It is up to them to decide what results to report and what results not to give.

In general, the researchers show a similar attitude, that is, they do not exclude women, but in many cases do not specify whether they have taken into account in their trials and, despite this, do not analyze the results obtained by sex.

When designing a clinical trial, the researchers try to have the smallest number of possible variables involved in the experiment.

From file

This was evident in a study by the Spanish Agency for Medicines and Health Products. He analyzed all the reports presented in the first quarter of 2007 to see if the participation of women in clinical trials was taken into account. It was found that only 20% of the 25 trials presented analyzed the results by sex or took into account the influence of sex.

Faced with these results, they could not say whether the participation of women was sufficient or not, since 80% of the investigations had not done so. The only conclusion they could draw was that the researchers did not take into account whether sex influenced the research they conducted, at least in the final report.

In fact, when these types of studies have been conducted, the results have been very varied, that is, they have not always found differences in the response of men and women to drugs. Sometimes they have found significant differences, but others have come to the conclusion that these differences are not worrying or that the answer is the same in men and women if the dose used is adjusted to body weight.

That is why it is essential to know whether or not there are differences. It would not be acceptable to generalize the effects. If there are no differences, we must prove that there is no difference, since there may be differences. Is not the scientific method based? A long process since a molecule invents it until it accepts it as a drug and, at the last moment, manages drugs to a part of the population without sufficient evidence.

Change with effort

The differences between men and women go beyond the sexual organs.

From file

Our society has not achieved, therefore, the famous equality between women and men in terms of clinical trials. For us to arrive, it is essential that researchers become aware of their importance.

It would be convenient for institutions to also bet on equality. It would be of great help if the legislation was modified and how clinical trials should be performed to ensure equality between men and women. Entities that grant grants can also collaborate by requiring that the results of grant projects be analyzed based on sex.

Outside the official bodies, scientific journals can have great strength -- the greater the name of a journal --. In short, it is appropriate for all researchers to make known the research carried out, to divulge to the maximum the results obtained. Well, if the journals consider it essential that in the experiments women are taken into account and that the results are disaggregated by sex when deciding whether or not the investigations are publishable, even indirectly, would force the scientists to design the experiments in this way.

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(Photo: R. R. Dans)

Clinical trials do not always end with the experiments performed in laboratories and hospitals. Sometimes, once all of them have been overcome, that is, when a certain drug is sold, researchers continue to study people who take it for a period of time. The objective is to know better the characteristics of the drug, discover possible new uses, etc. and to analyze people in conditions that could not be analyzed in previous phases. In this phase, the groups that have not been considered in the experiments are usually analyzed. Because they can alter the results of the experiments or endanger their lives, they also exclude older people and children from clinical trials as well as women.

Dilemma of pregnant women and medicines

The case of pregnant women is an extreme problem. In most cases, the effect of medicines on children is not tested with pregnant women. Of course, the risk of trying it is high, but not of not knowing which drugs can be used to treat diseases of pregnant women and what not. Therefore, during pregnancy women hardly receive medication and, when administered, sometimes they do not know if they will influence the fetus.

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In fact, most of the information available has been obtained in research carried out exclusively with animals. Scientists know that it is not certain that what is observed in animals is extended to humans, but many times they do not have the way to advance in the essay. For example, they realized this with the rubella vaccine. When tested on the monkeys, they saw that the virus did not cross the placenta. When they tested him with pregnant women (they tried volunteer women who wanted to abort), they saw that yes, the vaccine was passing through the placenta and infecting the fetus.

Infarctions and women, unknown tandem

Throughout the 1980s and 1990s, the idea had spread that women did not suffer from cardiovascular disease among physicians, and that their genes, hormones, or their own sex protected them. On more than one occasion, it has occurred that he had chest pain, left arm pain, or some other usual symptom before suffering a heart attack is that a woman who goes to the emergency room is told to have stomach problems or to be given sedatives or antidepressant drugs.

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With this background, it is no surprise that the methods of treatment of cardiovascular diseases are based on men. For example, in 1982, in a five-year research with 20,000 physicians, aspirin (acetylsalicylic acid) was shown to help prevent infarctions. They found that every day a certain dose of aspirin reduced heart rate by 44%.

Of course, the experiment was only with men. Twenty years later, in 2005, a study was conducted on whether women also did. They repeated the experiment with men with 40,000 healthy women. And there, they saw that aspirin did not act in the same way in women: before menopause, aspirin did not at all protect women from heart attacks, while menopause had the same influence as in men.