Can women trust the drugs that have only been tested on men?

Susan Jamison was 16 when she had a complete seizure at school. It had never happened before, though she had had a bad headache for weeks.

A neurologist diagnosed epilepsy and prescribed a high dose of sodium valproate: four 500 mg pills a day. The drug was considered effective and safe for preventing attacks. It worked for Susan, who is now 53: she has always taken it since.

Sodium valproate is prescribed in the UK under different brand names – Susan takes one called Epilim – and works by blocking the nerve activity in the brain involved in seizures. For some patients, this is the only medicine that works. It is also prescribed for bipolar disorder and as a last resort to prevent migraine.

Can women trust the drugs that have only been tested on men? Incredibly, that is the case for many of the most popular treatments on the market

Can women trust the drugs that have only been tested on men? Incredibly, that is the case for many of the most popular treatments on the market

For Susan, sodium valproate sounds like a success story. But the pharmacist's assistant and the mother of three say the drug has left behind all of her children, who are now 22, 24 and 26, with severe learning disabilities, psychological problems and physical disabilities – one child so serious that she will never live an independent life.

Susan was never warned that this could happen if she took the medicine while she became pregnant – although she had known of the danger by the time she had her first child for years. As many as 20,000 other children in the UK may have been affected in the same way.

& # 39; Nothing was told about birth defects when it was first prescribed or after. I only noticed that it was less effective for me to focus on lessons, & says Susan, who lives in Belfast.

Although the drug was widely prescribed (and is still given annually to around 27,000 women in the UK), sodium valproate was not specifically tested on women in 1963, let alone pregnant women.

This has been exceptionally the case for an untold number of other medicines, since women are nowadays often excluded from investigating the medicines they will eventually take.

This has created absurd situations. In the early 1960s, a study to see if estrogen supplements would protect postmenopausal women from heart disease employed 8,341 men and not women.

Heartache: Susan Jamison with children (from left) Joe, Caroline and Anna

Heartache: Susan Jamison with children (from left) Joe, Caroline and Anna

Heartache: Susan Jamison with children (from left) Joe, Caroline and Anna

Valium, that & # 39; mother & # 39; s little helper & # 39 ;, was never originally tested on women. But in a 2016 study in the Journal of Depression and Anxiety, Brazilian researchers revealed that the menstrual cycle can significantly change the effectiveness of Valium, depending on the time of the month – and even render it useless.

And before US regulators agreed to license controversial & # 39; female Viagra & # 39; drug Addyi in 2015, they asked for an investigation to see if it was safe when taken with alcohol. The drug sponsor conducted a test of 25 people, including 23 men. That was double absurd, because women are known to be more susceptible to the effects of alcohol, even if it is not mixed with a sex drug.

They are not just treatments. A recent American study into how obesity affected breast and uterine cancer did not register for one woman.

Researchers prefer men

Why are male bodies preferred? The main reason is that women's monthly cycles cause hormonal fluctuations that can complicate the results of the clinical drug tests that are required before a new drug is approved for use. Researchers and pharmaceutical companies prefer male bodies because they are much simpler.

In addition, women of childbearing age (and pregnant women) have traditionally been excluded from drug safety trials for fear of violations of fetuses. Instead, drugs have come on the market in what is, in fact, a gigantic random test, in which later hard evidence of damage to children can arise – and may not be taken seriously, ignored or covered.

This practice has caused untold damage to women and their families.

When Susan had her first child in 1992, Caroline, it was immediately clear that something could be wrong.

& # 39; She was born with a strange facial expression, & # 39; Susan remembers. Her ears were small and her eyes seemed far apart. The pediatrician looked at her and asked if I had taken sodium valproate. I answered "yes" but nothing more was said. I thought it was a passing question whether I was taking my medicine for epilepsy and I no longer thought about it. & # 39;

Caroline was developing very slowly and only started walking after 19 months. Her speech was also much delayed. Her deep-lying characteristics, developmental delay and subsequent autism were in fact classical signs of fetal valproate syndrome (FVS). It was first identified in 1984, the year neurophysiologists at Aston University in Birmingham reported how the drug could cause spina bifida in babies, among other abnormalities.

Clinicians who worked there warned all women about the risks and said they should stop taking the drug a month before trying to conceive. But the warning did not spread to clinicians or female patients who, unaware of the risks, fell through while taking the drug. Susan was one of them.

Her second child, Anna, was born in 1994.

& # 39; She appeared to be the hardest hit, with low intelligence, ADHD and dyspraxia & # 39 ;, says Susan. & # 39; Anna developed Asperger's syndrome and had to go to a school for special needs.

Dozens & # 39; sexist & # 39; drug testing

VALIUM

& # 39; Mothers little helper & # 39; was not tested on women before it first appeared on the market, but recent studies have found that changes in the menstrual cycle may render it unusable.

ADDYI

A study into the interaction between alcohol and the so-called female Viagra registered 23 men and only two women.

THALIDOMIDE

The original medicine for the birth scandal was never tested on pregnant women before it came on sale in 1957 for morning sickness. It was found in 1962 to catastrophically disrupt the development of the fetus.

DIETHYL STILBESTROL (DES)

This synthetic form of estrogen was widely prescribed between 1938 and 1971 for pregnant women to prevent miscarriage. Later this proved to be ineffective – and in 1971 it appeared to increase the risk of specific cancers in women.

TAMIFLU

Research in 2011 suggested that pregnant women remove the drug from their bodies faster, so that expectant mothers may have received too low doses.

& # 39; She is now 24 and will never be able to live independently. She has an emotional age of four and will always need care that I provide. & # 39;

Again, no one ever said that Susan & # 39; s epilepsy medication was the cause. & # 39; The doctors have just asked if there were similar problems in my family. There were none, & she says.

In 1994 she became pregnant with her youngest, Joseph. He was born prematurely after 31 weeks, which Susan thinks is also related to Epilim. He had intensive care with respiratory problems for a month.

Joseph is now 22 and works for a large retailer. & # 39; He has ADHD and dyslexia. His behavior can be challenging, he can find life gloomy and lonely, "says Susan. & # 39; But he has a high IQ of 139 and is great with computers and musical instruments. What could he have done with his talents, were it not for his birth problems? & # 39;

For years Susan wondered why her children had been affected this way. The cent did not fall until February last year, when her pharmacy received leaflets explaining how Jeremy Hunt, then health minister, launched the Independent Medicines and Medical Devices Safety Review to how the NHS responded to birth damage caused by sodium valproate.

Studies show that babies born by mothers who used the medicine during pregnancy have a 10 percent chance of having a physical birth defect and a 40 percent chance of having learning and developmental problems .

Tragically, sodium valproate is not an isolated case.

Maya Dusenbery, an American journalist who has investigated these shortcomings in a book titled Doing Harm, says that the tendency for women to penetrate everything in medical research.

& # 39; It starts with the most basic biomedical research, where researchers in pre-clinical studies use overwhelmingly male cells and male animals, & she writes. & # 39; It remains throughout the entire clinical trial process, with women remaining underrepresented, the analysis of drug-response differences is rare and the different hormonal states and cycles of women are usually completely ignored. & # 39;

Female fat slows down medication

Under the microscope: the British boxer Amir Khan, 32, answers our health quiz

British boxer Amir Khan answers our health quiz

British boxer Amir Khan answers our health quiz

British boxer Amir Khan answers our health quiz

Can you run up the stairs?

Yes, I train a lot with steps. When I'm not boxing, I'm more focused on cycling and running to give my upper body a break.

Do you receive five a day?

I am a very large fruit and vegetable eater. I like to make vegetable and fruit juices. I put beetroot, celery, cucumber, broccoli and spinach in a vegetable juice. I can also add garlic. I think that juices help the body recover itself after heavy training sessions.

Pop pills?

The last time I took a painkiller was in 2016, after surgery to fix my hand. But I take vitamins. Before I go to a training camp, I have my blood tested to find out what deficiencies I have so that I can sort them. I am a fan of vitamin C and D supplements.

Ever been on a diet?

Always. I have a cook who cooks for me. I am 1.74m (5ft 7in) tall and my fighting weight is 67kg (10pcs 7lb). Normally, however, I am around 11th 7lb. It's hard to stay in shape all the time.

All the vices?

I crave sweets. If you train so hard that you burn a lot of energy, you want something sweet.

Have you ever had plastic surgery?

If I broke my nose in a fight, I had surgery to fix it, but it's already confused with all the punches it has made. Maybe when my career is over, I'll fix it.

Most serious illness?

I broke a bone in my hand early in my career and immediately went back to training without repairing it, so it only got worse. In 2016, I had a two-hour operation in which the bone was removed from my hips and used as an implant to repair the right hand, placing seven screws. I have fought twice since and won both periods.

All family ills?

My paternal grandparents had type 2 diabetes.

Handle pain well?

My tolerance is really good. I take punches for a living, that's how it should be.

Is sex important?

I think it must be in a relationship.

Have you ever been depressed?

Never. I think ups and downs happen to us all.

What keeps you awake?

Nothing. I can sleep anywhere. I normally have eight hours a night, but I love ten hours if I can.

Phobias?

Snakes. I was in I & # 39; m A Celebrity. . . in 2017 and encountered two.

Do you like to live forever?

No. When it's time to go, it's time to go. Enjoy life.

  • Amir Khan recently released & # 39; Ring the Changes & # 39; launched with thinkmarkets.com to support disadvantaged young people.

For years there has been an assumption that women – like doctors have been joking for a long time – just & # 39; men with breasts and tubes & # 39; who respond to men in the same way as men.

Drug triallers simply hoped that pregnant women – or rather their unborn babies – would react in the same way as men.

However, the differences between male and female bodies can strongly influence the efficacy and possible side effects of medicines.

Large population studies show that women have considerably more serious side effects than men. Often this is because they take recommended doses based on male bodies, although they are generally smaller and their metabolism can shed the drugs more slowly.

The fact that women have more body fat than men can cause serious changes in their response to drugs, especially those that are soluble in fat and therefore likely to remain in their system for longer.

The popular sleeping pill zolpidem (brand name Ambien) was approved for safety in 1992. But more than 20 years later, studies revealed that the dosage instructions for women – the same as the male dose – were twice as high as they should be.

This was because the fat-soluble medication remained in their body for much longer, making them sleepy in the morning and there was a risk of car accidents.

The US Food and Drug Administration (FDA) halved the dose for women in 2014, but evidence shows that she knew about the problem in 1992 when she received clinical data showing that the amount of Ambien in a woman's blood was 45 percent more then was in a man.

Even the use of male mice in early safety tests can produce results that ultimately threaten women. Two years ago, scientists from the British Wellcome Sanger Institute reported in the journal Nature Communications that gender differences can seriously affect the results in more than half of the experiments.

Indeed, research from McGill University in Montreal, published in 2015, showed that male and female mice process pain signals differently.

About 80 percent of the chronic pain studies have used male mice, but 70 percent of those who suffer such pain are women.

In 1977 the practice for non-women in early phase of safety testing became official policy, with the FDA women of & # 39; fertile age & # 39; forbidden to participate. Where the US led, the world followed.

This apparent intention to protect women has exposed them to a much greater risk when the drugs come on the market. In 2001, the US Government Accountability Office reported that 80 percent of the prescription drugs that were no longer used in the last three years were removed because they posed a greater health risk to women.

These include antihistamines such as Seldane (generic name terfenadine), the type 2 diabetes medicine Rezulin (troglitazone) and the heart medicine Posicor (mibefradil dihydrochloride). Their previously unknown side effects include potentially fatal damage to the heart, liver and intestines.

Uterine cancer screening in men

This delay in investigating and communicating health risks that women are confronted with in a unique way goes beyond drug research alone.

A study at Rockefeller University in New York into how obesity affected breast and uterine cancer did not enroll women. Leon Bradlow, a scientist working on the 1986 project, told reporters that men could study cheaper because their hormonal systems were easier.

This attitude has expanded to other crucial areas.

Clinical evidence has shown that women can fully distinguish the symptoms of a heart attack from those of men. Often women do not experience the characteristic male sign of chest pain, as experts say their symptoms are driven by different mechanisms. Instead, they may experience nausea, stomach pain or jaw pain.

Nevertheless, the NHS Choices website continues to refer to chest pain as the primary symptom and does not mention female signs.

Such ignorance explains why a November study in the Heart magazine found that women in England and Wales are twice as likely to die in the 30 days after a heart attack than men.

University researchers at the University of Leeds said women were less likely to receive treatments such as medicines and surgeries in time to save them. Many were told that nothing was wrong and were sent home.

Professor Vera Regitz-Zagrosek, the EU coordinator of European projects on gender medicine, says that it appears that women's heart attacks are controlled by different physical mechanisms, since estrogen and testosterone act in different ways on the cardiovascular system. But the specific mechanisms that fuel women's heart attacks often remain a mystery, she adds, because there is a lack of research, a lack of research funding, a lack of animal models and a lack of researchers who understand these problems & # 39 ;.

Attempts to tackle such inequalities began in 1993, when Bill Clinton, the US president, signed a law requiring government-funded investigations to include enough women to ensure a & # 39; valid analysis & # 39; of any difference.

Changing, but not fast enough

But in 2015, Carolyn Mazure, director of the Yale School of Medicine research center for health research, concluded in BMC Women & # 39; s Health magazine that progress over the past two decades is painfully slow & # 39; used to be.

At least the dangers of sodium valproate are now being taken seriously. In the UK, health secretary Jeremy Hunt Barones instructed Julia Cumberlege, a former health minister, to investigate why growing evidence of the serious risk of pregnancy was not disclosed to patients.

This month, the UK Medicines and Regulatory Healthcare Products (MHRA) regulator tightened & # 39; pragmatic & # 39; guidelines established for doctors prohibiting the use of sodium valproate for women of child-bearing age unless there is no alternative, in which case women should be put on a strict contraceptive program.

Such guidance is welcome, but can be difficult for practitioners to fulfill, says Louise Howard, professor of Women & Mental Health at King & # 39; s College in London. & # 39; After all, & # 39; she says, & # 39; about half the pregnancies in such a & # 39; n patient population are not planned. & # 39;

In the meantime, we are confronted with a potentially toxic legacy of other drugs that may contain hidden damage to women or their unborn children, as they were only tested on males, males or male tissue samples in clinical safety studies. Professor Howard says that tackling this is a very difficult task because the damage can be hidden in the banknotes of patients scattered across the country like giant dot-to-dot puzzles that have never been put together.

& # 39; We need investment in research to get a good idea & # 39 ;, she says. & # 39; There is more interest to think about this, but not much research in the UK. And unfortunately the available information is not sorted properly. & # 39;

As well as trying to unravel past mistakes, Professor Howard wants to put an end to the practice of focusing on male bodies and brains in clinical studies.

& # 39; For the well-being of women, & # 39; she told Good Health, & # 39; we need research funders to ensure that studies and data are gender sensitive. & # 39;

Meanwhile, Susan tries to stay philosophical about her problems. & # 39; My children will always struggle and I will always bear the blame & # 39 ;, she says.

& # 39; I wish I had been warned. & # 39;