IF YOU are pregnant or breast-feeding, think twice before reaching for the aspirin or paracetamol. A study has shown that male rats exposed to such drugs in the womb or just after birth have little interest in sex as adults, raising the question of whether these drugs also affect human sexual development.
When newborn male rats were given two injections of a drug called indomethacin (Indocin), they had a much lower libido than normal when full-grown. Similar but milder effects were observed in male rats whose mothers drank water containing aspirin for seven days before birth and seven days afterwards.
Aspirin and indomethacin belong to a class of drugs called COX-2 inhibitors, which also includes paracetamol (Tylenol). Indomethacin is used to prevent premature labour, while low doses of aspirin may be prescribed during pregnancy to reduce the risk of pre-eclampsia.
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However, the researchers and other experts say it would be premature to change women鈥檚 medication on the basis of this rat study alone. 鈥淚 don鈥檛 want to panic pregnant women,鈥� says Margaret McCarthy of the University of Maryland, Baltimore, who carried out the study along with colleague Stuart Amateau. The best advice remains for mothers-to-be to avoid unnecessary medication.
Melissa Hines, an expert in the neural basis of sexual behaviour at City University, London, points out that maternal stress in rats can also cause changes in the sexual behaviour of their offspring. But the same does not happen in people. 鈥淚 don鈥檛 think we can say anything about humans based on this,鈥� she says.
If there are any effects on babies, they would become apparent only after puberty, making it difficult to establish whether or not these drugs affect human sexual behaviour. However, a long-term epidemiological study of 15,000 children born in the UK in the early 1990s, called the Avon Longitudinal Study, might provide the answer.
Hines has already looked at gender roles in some of these children, such as whether or not girls become tomboys, and is now re-examining the data to see if there is any link with exposure to COX inhibitors. She also plans to do a follow-up study based on a questionnaire about sexuality. Meanwhile McCarthy plans to repeat the rat experiments in non-human primates.
Whatever the results of these studies, the work is a significant step forward in understanding how testosterone masculinises the growing brain, says Marc Breedlove, a neuroscientist at Michigan State University in East Lansing. 鈥淭his is currently a black box,鈥� he says.
McCarthy and Amateau have shown that testosterone 鈥� the 鈥渂e a man鈥� signal 鈥� boosts production of a molecule called prostaglandin-E2 (PGE2). This in turn causes structural changes in a region of the brain called the preoptic area, which is implicated in sexual behaviour (Nature Neuroscience, DOI: 10.1038/nn1254).
The team proved this by injecting some female rat pups with extra doses of the prostaglandin. As adults, these females behaved just like males, attempting to copulate with other females just as often as normal males. COX-2 inhibitors affect sexual development, at least in rats, because they block PGE2 production.
The finding is a surprise because prostaglandins are usually associated with pain and inflammation. 鈥淭here was no indication that they were involved in brain development or sex-specific effects,鈥� says McCarthy.