Oxytocin: love in the air, junk in the literature

by Professor Gareth Leng

volesA beautiful story, from a host of elegant work on voles, has popularised the idea that oxytocin released in the brain is a “love hormone”, instrumental in forming long term bonds between sexual partners. Understandably, a huge amount of interest has been aroused about whether oxytocin has similar effects in man.

One of the first studies of oxytocin and sex was reported by Geoffrey Harris – the “father of neuroendocrinology” – in Nature in 1953. His colleague Vernon Pickles, while studying lactation, had reported the case of a lactating woman who had experienced milk let-down immediately after achieving orgasm, and together Harris and Pickles set about seeing if this was a common occurrence.  Their approach was wonderfully direct – they asked the wives of their colleagues. Six of these had noticed milk let down during some stage of coitus, and another two reported the ‘tingling experience’ in their breasts that they recognised as the same as they experienced during suckling. Milk let-down is a reflex for which oxytocin is essential, and so this “bioassay” was powerful evidence that oxytocin is released during coitus.

There is a temptation to think that modern analytical techniques are much more specific and reliable than bioassays, which infer the presence of a substance by observing its biological effect. Unfortunately this is often not so. The modern way of measuring oxytocin in the blood is by immunoassays which infer the presence of substances from interactions with antibodies to that substance. However, while antibodies to oxytocin certainly bind oxytocin, they also bind other substances in blood that are wholly unconnected to oxytocin. This problem has long been recognised, and is easily avoided by purifying the samples to extract these interfering factors before samples are assayed.

Unfortunately, many papers have been published recently using a commercially available ELISA assay without first extracting their samples. These studies have reported measurements that are several hundred fold higher than validated measurements in extracted samples, and the reported results are thus, to say the least, highly questionable. Amongst the most blatant examples of this poor practice are many studies that attempt to relate measurements of oxytocin in the blood to aspects of social behaviour in man.

In response to caustic criticism, the manufacturers of the assay have now “strongly recommended” that users should extract blood samples, but to date none of the many studies using this flawed methodology have been retracted. Perhaps the authors hope that the measured levels correlate with authentic oxytocin levels, but this hope seems vain. Three studies have now compared ELISA measurements of oxytocin in the same samples with and without extraction; all three reported no correlation at all.

There are several worrying aspects of this. First, these problems have been highlighted within the field for several years, yet papers are still being published with this discredited methodology. Second, no papers have been retracted, despite the clear acknowledgement of the problems by the manufacturers of the assay. Third, it is startling how easy it seems to be to draw an apparently meaningful conclusion about oxytocin from measuring something wholly unrelated to oxytocin.

The reliability of the scientific literature has come under a storm of criticism in recent years, and the concerns extend to the most established of journals.  These concerns include psychological research, about which a recent paper bemoaned the abundance of “questionable researcher practices, resulting in the promulgation of theories that are ideologically popular but have little basis in fact.”

Problems with the integrity and validity of research published in the scientific literature are widespread and multi-faceted, and have many different causes. They will not be eliminated quickly, but as a start, the editors of journals that claim high standards might take steps to strip from their pages papers that are demonstrably junk. A start might be to seek retraction of papers whose conclusions depend on oxytocin measurements made with invalid techniques.

Gareth pic

Fluorescent imaging of oxytocin cells and fibres in the supraoptic nucleus of the hypothalamus. Image credit V. Tobin.

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