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Men, women and drugs

David Hughes and gender-specific medicine

Most experimental drugs are tested only on men, and two thirds of illnesses affecting both sexes are likewise studied only in men. Yet men and women are different in more than the obvious ways.

Although women are usually smaller than men, they receive the same dosage advice for most medicines, which can lead to a higher concentration of a drug in the system, particularly as men and women metabolise medicines at different rates.

And women have a higher amount of body fat the men, so if the drug is lipophilic- attracted to fat cells- it will move into those tissues and remain in the body for longer.

This is already recognised in the advice given for safe thresholds of alcohol consumption- less for women, who metabolise alcohol more slowly. So do one-size-fits-all prescriptions for adults risk some of us taking too little medication- or too much?

It's certainly a possibility, and one which researchers are rapidly seeking to explore. As far back as 2001, a study found that 11 percent of women who were hospitalised were there because of incorrect medication, while another study discovered that women seemed to suffer from side effects of medication 50 percent more than men.

Between 1997 and 2001, eight out of ten drugs banned by the US Food & Drugs Administration (FDA) posed greater health risks for women than for men.

In 2013, the FDA issued their first sex-specific dosage guidelines when they recommended that women should take only half the usual dose of the country's most popular sleep drug, Ambien, as they were waking up still drugged & drowsy.

Why? Because men and women metabolise medications at different rates, which was leading to women having up to 45 percent higher concentrations of the drug in the bloodstream. The FDA had known about the 45 percent difference for 20 years, but hadn't realised that it mattered- so for those years, many women effectively overdosed on sleep medication, taking significantly more than they needed.

Gender differences in how we respond to medication is an emerging but fascinating field, and one which may lead to different dosages for men and women, and more effective treatment. What we know so far includes:

Heart disease

Much of the current advice is based on studies that were done only on men; a case in point is the suggestion that a daily aspirin will protect against heart disease, where studies were done on men,. Evidence now indicates that aspirin protects men better than women against heart attack, but women better than men against stroke. Likewise with statins, where recent studies indicate that men have fewer heart attacks and strokes, but that women may gain only half the same benefit.

Antidepressants

When it comes to antidepressants, women respond better to SSRIs- selective serotonin uptake inhibitors- while men may fare better with tricyclic antidepressants.

Serotonin is a natural substance and a known antidepressant, and women produce less of it than men.

SSRIs may be absorbed more quickly in women because of lower stomach acidity, which can help them to feel the effects more powerfully and it's been suggested that the drugs could be more toxic to women at standard doses.

Valium, often prescribed for anxiety, is broken down faster in the body of women than men, making it less effective- yet dosage advice tends to be the same for both sexes.

Men's kidneys filter out drug compounds faster than women's which suggests that women should wait longer than men before taking a second dose, particularly of benzodiazepines.

These benzodiazapines are designed to dissolve in fats to pass from the bloodstream in tothe brain; as women have more body fat, these drugs may linger in the system for longer.

Digestion and elimination

Stomach acidity is lower than in men, which means that the active ingredients in medicines absorb for longer in the stomach. Enzymes in the stomach lining and liver, which help remove excess medications from the body, behave differently in men and women; and for older women in particular, kidney function tends to decline, which may lead to higher concentrations of active ingredients remaining in the body.

Painkillers

There's current concern about the risk of addiction to powerful opioid painkillers, so it's interesting that initial studies suggest that women may get a more powerful effect from them than men, which may enable them to take a lower dosage. Men appear to respond better to NSAIDs- non-steroidal anti-inflammatory drugs.

Anaesthetics

Men and women respond differently to anaesthetics because off the different distribution of fat in the body. Women respond better to water-soluble anaesthetics, while men respond better to fat-soluble ones such as Propofol.

Blood Pressure

The same A43 enzyme in women which reduces the effect of Valium can actually make the effect of other medications stronger, including losartan, taken for high blood pressure, this increasing the risk of blood pressure that is too low.

Antipsychotics

Drugs such as haloperidol seem to be more effective in treating hallucinations and delusions in women than in men.

Anticonvulsants

Research suggests that a number of liver enzymes work at different speeds in men than women; this is thought to be why some drugs, such as anticonvulsants, are less effective in women than in men.

The future

in the US, the FDA has promised to step up its efforts to account for sex differences in clinical trials, and both there and in this country we can expect to see more evidence emerging about the different responses of men and women to the same srigs, and consequently a more accurate set of guidelines about effective dosages.

In the meantime, it's always worth flagging up to subject with your GP when being prescribed a medicine. Has the drug been treated exclusively on men, and if so, would a lower dose for a woman perhaps be more appropriate?

It's worth asking. And for the highly motivated, there is always the prospect of taking part in clinical trials as the field of gender medicine becomes more and more established.

Ultimately, it should be possible to prescribe the right medication in exactly the right dose, taken at the right time; and understanding the complex differences in the way men and women respond to the same medication will go a long way to achieving that.

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