Blue genes
If body physiology differs between males and females, it follows that the activity of genes should be different too.
Males and females have the same genes, except for those few extra genes present on the male-specific Y chromosome. Most of these are needed to build male body parts, such as the testes.
But it is not just the presence or absence of genes that is important in biology: also crucial is when and where they are active.
In fact, this has not been extensively studied and very little is known about sex differences in gene activity. Some differences have been seen in different regions of the brain and in the kidney in animal studies. It is not clear which differences are most important, however.
Not surprisingly, significant differences are seen in gene activity in ovaries and testes (which share the same origins in the early embryo). Several hundred genes are more active in one or other organ. Interestingly, some genes less active in testes than ovaries are involved in immune responses. The male gonad (but not the female) seems to be immunosuppressed, though no one knows why this is necessary.
Liver gene pool
One organ where sex differences in gene activity have been linked to biological effects is the liver. One of the liver's most important roles is in ridding the body of toxins. Central to this activity are an important set of enzymes, the cytochrome P450s. These enzymes metabolise hormones, drugs and toxins.
It is possible that variation in human cytochrome P450 gene activity could explain sex differences in responses to pharmaceuticals – for example, at least 31 drugs metabolised by the CYP3a family of cytochrome P450s are cleared faster by women than men.
The differing gene activity in the liver may be driven by sex differences in growth hormone release. In males and females growth hormone release is cyclical, but the pulses are more common and smaller in females. The molecular mechanisms underlying this difference are beginning to be clarified.
How important are these differences? In some cases, doses of drugs do need to be tailored to someone's sex. For example, women's heart rhythms differ slightly from men's. Drugs that affect heart rhythm as a side-effect (as a number do) can be particularly hazardous to women.
Whether this is an exception or highlights a general need to identify the effects of drugs separately in men and women is still debated. Some say that, overall, the effects of sex are part of a broad range of responses in different people. Others argue that the differences are big enough to matter. For example, in a recent study of nearly 20 000 hospital admissions, women accounted for 52 per cent of all admissions but 59 per cent of admissions for adverse drug reactions.
Brainy genes
What about that most critical organ, the brain? In mice, the activity of around 50 genes seems to differ in male and female fetuses. In the adult, very few differences have been found, even in areas that differ significantly in structure.