Meeting halfway: the untapped potential of gender-specific drugs

The biological differences between men and women extend far beyond the obvious reproductive ones. rbrwr/flickr

Personalised medication is one of the ultimate goals of modern medicine although it’s still some way off. But the promise of gender-specific medicines means we may soon be halfway there.

In its purest form, personalised medicine would create treatments for each person based on their individual biochemistry and physiology, improving chances of success and reducing potential risks.

But while it’s a noble goal, the potential difficulties are obvious. Not only does personalised medicine require a fundamental change to our health-care system, the costs involved in creating individual treatments would be substantial. So it may be decades before we see truly personalised medicines.

The halfway point between the current system and personalised medical care are gender-specific medicines, that is, different drugs or different forms of a drug for men and women.

Nearly there?

The biological differences between men and women extend far beyond the obvious reproductive ones. And a recent study provides (further) evidence in support of developing different drugs to treat disease and illness in the two sexes.

The study, published in PLoS Genetics, showed that concentrations of more than three-quarters of the molecules found in cells are significantly different between men and women.

Known as metabolites, these small molecules are found in a given cell, tissue or fluid, and their study is called metabolomics. Metabolites include amino acids, sugars, fatty acids and lipids, and most studies aim to profile as many of such molecules as possible in a single analysis.

The field of metabolomics has expanded substantially in the past decade and is beginning to make a major impact in clinical studies. It has many applications, including detecting disease and monitoring progression, studying responses to environmental conditions and determining people’s responses to treatment.

Gender differences

The variation between men and women is primarily influenced by genetic and hormonal factors. Other differences that could influence gender-specific responses to a drug include body size and fat levels, and differences in the digestive system and liver function.

But the idea of gender-specific medical treatment is not new. Differences in male and female responses to some drugs was first noted in 1932 and known examples of this variation abound.

Female subjects typically require half the dose of barbiturates to induce sleep, for instance, and usually sleep substantially longer.

But concerns over hormonal variations due to the menstrual cycle and the possibility of pregnancy meant that women of childbearing age were actively excluded from early-phase clinical trials in the United States until 1993.

A 1992 study reported that for over half of new drug applications from 1988 to 1991, the FDA did not seek any sex-related information on the drug’s safety.

And the 1993 legislative change to oblige the FDA to consider such information was shown to be well founded when a 2001 study revealed eight out of ten drugs that had recently been removed from sale showed greater adverse effects in women.

A history of segregation

Not only have drug trials historically excluded women, but many clinical disease studies haven’t included female subjects.

So not only is there a lack of knowledge about how drugs work, there are also gaps in our understanding of how diseases differ between the sexes.

Another important consideration is that in many developed countries, women take more prescription medications than men. But the lack of clinical data on the female response to drugs means that medical practitioners often have to estimate the appropriate dose.

Of course, there are already some drugs that are designed to specifically treat men or women, although most of these are related to reproduction. They include contraceptive pills, the controversial abortion drugs and male virility drugs such as Viagra.

Another gender-specific medicine already in use is Herceptin, which is used to treat breast cancer. Indeed, patients must be screened before the drug is given to ensure that their tumour contains the target defective gene product, HER2.

So gender-specific medicines that we have mostly target conditions that only affect one of the sexes. What we are yet to see are different forms of a given drug that are optimised differently for treating men or women.

It’s clear many gaps in our knowledge need to be filled before we can truly start to develop gender-specific medicines. But advances in fields such as metabolomics mean we are better equipped to fill them in the near future.