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2716 S. C. Roberts et al. MHC, odour and oral contraceptives
Table 1. Mean scores given to three MHC-similar and three MHC-dissimilar male odours by 110 normally cycling women
tested during the late follicular phase (session 1). The core sample excludes non-UK women and shirts worn by non-UK men or
those that were noted by the participant as smelling of tobacco smoke or fragranced products.
meanGs.e.
when analysis was restricted to the core sample of British the core sample (nZ52, tZ1.06, 0.38 and 0.27, all n.s.;
women and shirts not perceived as smelling of tobacco electronic supplementary material, table S4). We found no
or perfumed products. Across all ratings, there was no effects of male heterozygosity on odour pleasantness,
correlation between allele sharing and either odour intensity or partnership desirability; mean pleasantness/
pleasantness (rsZK0.002, nZ660, pZ0.95), partner desirability scores were higher for heterozygotes in non-
desirability (rsZ0.013, nZ659, pZ0.73) or intensity users, and lower in pill users, but these differences did
(rsZK0.046, nZ659, pZ0.24). not approach significance (electronic supplementary
In session 2, where some women were using the pill, we material, table S5). Following Wedekind et al. (1995),
again found no significant differences in any comparison we tested for an association between MHC dissimilarity
(electronic supplementary material, table S3). Our results and the number of times women indicated that shirt
therefore suggest that, at least in our sample, there was odours reminded them of either partners or relatives.
neither a significant general preference for MHC dissim- However, we found no significant effects in either session
ilarity across normally cycling women, nor a significant (electronic supplementary material, table S6).
preference for MHC similarity associated with pill use.
We checked whether the non-significant effect (d) Changes in relation to pill use
described above might be owing to the inclusion of a Although we detected no general MHC-associated
proportion of men who, across the sample, were assessed preferences, we next looked for potential shifts in
only under one condition (i.e. only as a MHC-similar/ preferences across sessions. We first calculated a within-
dissimilar man). This might be a problem if the odours session difference score between mean ratings of MHC-
of such men were unusual or especially (un)attractive. Of similar and MHC-dissimilar odours for each rater,
all shirts rated in this experiment, 47 were from men subtracting similar scores from those for dissimilar odours
assessed only as MHC similar, and 48 from men assessed (positive scores indicate preference for MHC-dissimilar
only as MHC dissimilar (7% each; the other 86% of shirts odours). We then used doubly multivariate repeated
were from men assessed by at least one woman in both measures ANOVA to test for changes in relative preference
MHC-similar and MHC-dissimilar conditions). There for MHC dissimilarity.
were no differences in odour pleasantness, desirability or We found no significant main or interaction effects
intensity between these men (independent-samples t-tests, when using the whole sample. However, with the core
all pO0.17). Furthermore, recalculating mean MHC- sample, we found a significant session–group interaction
similar and MHC-dissimilar ratings for each woman, (F3,71Z3.05, pZ0.034), driven mainly by desirability
with these men excluded, had little effect on the results ratings (F1,73Z3.63, pZ0.061; pleasantness F1,73Z0.22,
(compared with table 1: pleasantness, t109Z0.32, pZ0.75; pZ0.64; intensity F1,73Z0.01, pZ0.92). Excluding
desirability, t109Z0.24, pZ0.81; intensity, t109Z1.98, the one woman who used a progesterone-only pill did
pZ0.051; core sample: all pO0.4). not affect the main interaction (F3,70Z3.07, pZ0.034)
Following previous studies ( Wedekind et al. 1995; but increased the effect of desirability ratings (F1,72Z4.19,
Wedekind & Füri 1997), we next compared scores pZ0.044). This interaction (figure 2) is indicative of
assigned to male shirts when presented to MHC-similar a decreasing preference for dissimilarity across the
and MHC-dissimilar women (i.e. men as unit of analysis). two sessions among the pill-using group and, to a lesser
In this analysis, we used z scores (i.e. with a mean of zero extent, an increasing preference for dissimilarity in the
and standard deviation of 1) to control for variability in the control group.
use of the rating scale by individual women (cf. Roberts Finally, we considered the possibility that differential
et al. 2005b; full details, also using raw scores, are given use of the rating scale between sessions might obscure any
in the electronic supplementary material, table S4). In relevant effects (e.g. women’s familiarity or distaste for the
session 1, we found no difference in ratings when odours may have changed as a result of experience in
individual men’s odours were assessed as MHC similar session 1, and might have differed between the pill
or MHC dissimilar, neither in the entire sample (paired and control groups). We therefore repeated the analysis
t-tests, nZ79 men, tZ0.54, 0.35 and 0.93 for pleasant- using z scores. This made little qualitative difference to
ness, intensity and desirability, respectively, all n.s.) nor the analysis, again showing a significant session–group
0.6
3.8
difference (dis–sim)
0.4
3.6
mean score
0.2
3.4
0
– 0.2 3.2
– 0.4
3.0
paired single
(b) 0.8
relationship status
0.4 4.5
0
3.5
– 0.2
3.0
– 0.4
2.5
(c) 1.0
2.0
0.8
occasionally rarely never
0.6 extra-pair fantasy
difference (dis–sim)
preference, but among women in relationships, we report significant effects of MHC on odour perception
found a near-significant association between MHC- (e.g. Santos et al. 2005). Although not specified in
odour desirability scores (but not pleasantness or Wedekind et al. (1995), Wedekind & Füri (1997) noted
intensity) and the frequency with which women reported that odour donors had unshaven axillae and that odour
fantasizing about sexual relationships with other men collection occurred during the summer. We did not collect
(F2,45Z2.68, pZ0.080), such that women who did so information on axillary shaving (but few British men do
more frequently gave higher desirability scores to MHC- so) and shirt wearing took place all-year round. We did not
dissimilar odours (figure 3b). use untreated cotton shirts (although shirts were washed
There was no significant association between intention with unperfumed detergent) and used halved rather than
to initiate pill use and current relationship status: 22/41 whole shirts, which may have reduced stimulus intensity.
pill users and 40/72 non-users reported being in a We used glass jars rather than cardboard boxes to present
relationship (X 2Z0.45, pZ0.85). Despite this, in view the shirts, and capped these with aluminium rather than
of the effect of relationship status, we repeated the main plastic foil, because glass can be washed and plastics
repeated-measures analysis of pill use on ratings, this time absorb odours. Finally, we asked women to briefly sniff all
adding relationship status as a between-subjects factor. shirts before undertaking rating, which Wedekind et al. did
The results remained qualitatively unchanged: there was not, because we felt this would allow women more
a significant session–group interaction (F3,69Z2.95, consistent assessment of the shirts and reduce order
pZ0.039), driven by odour desirability (F1,71Z3.53, effects. While some further differences were introduced
pZ0.064), but no significant interactions for session– owing to our more complex experimental design, most
relationship status (F3,69Z0.46, pZ0.712), relationship were intended as improvements on design, although it
status–group (F3,69Z0.45, pZ0.717) or session– remains possible they may have obscured women’s ratings.
relationship status–group (F3,69Z0.04, pZ0.990). A more serious methodological difference was that,
There was no relationship between self-rated attrac- while Wedekind et al. (also Thornhill et al. 2003; Santos
tiveness of women raters and pill use (Mann–Whitney et al. 2005) presented freshly worn t-shirts to their
tests; facial attractiveness: UZ1254, pZ0.82; physical smellers, we stored shirts in a freezer between collection
attractiveness: UZ1174, pZ0.44; both nZ39pill and and presentation. However, Thornhill et al. found no
66non-pill). Self-rated facial attractiveness did not vary significant preference related to MHC, suggesting that a
among single or paired women (UZ1349.5, pZ0.90, null effect cannot solely be attributed to freezing.
nZ57single and 48paired), but self-assessed physical attrac- Conversely, other odour studies using frozen samples
tiveness was higher among paired women (UZ1056.5, have detected predicted and biologically meaningful
pZ0.038). However, tests of MHC preference in the effects, such as the relationships between odour and both
first test revealed no effect of physical attractiveness facial attractiveness and bodily symmetry (Rikowski &
(entered as a covariate) on preference either in a model Grammer 1999), ovulatory status effects on women’s
without relationship status (main effect, pZ0.37; odour attractiveness (Singh & Bronstad 2001), and of
interaction pZ0.70) or with it (main effect, pZ0.44; particular relevance here, the ability of human smellers to
interaction pZ0.42; the MHC–relationship status inter- detect genetic relatedness through body odour (Roberts
action remained significant, F1,77Z4.17, pZ0.045). et al. 2005a) and of a perfumer to describe MHC-
Including self-rated attractiveness (either facial or physi- associated odours (after freezing for more than 1 year:
cal) as a covariate in the main repeated measures ANOVA Wedekind et al. 2007). Furthermore, while the predicted
across tests only increased the significance of the positive effect of MHC dissimilarity on ratings was not
session–group interaction reported above (F3,66Z4.18, supported, we did detect other differences associated with
pZ0.009 and F3,66Z3.45, pZ0.021, for facial and pill use and relationship status, and ratings within and
physical attractiveness, respectively). between test sessions were highly repeatable. Our supple-
mentary experiment using frozen t-shirts from the same
men found no significant effect of freezing over 3 months
4. DISCUSSION on odour ratings or preference rank. Thus, though it
Although several studies have reported significant effects of remains a possibility, we think it unlikely that frozen
MHC dissimilarity on women’s preferences for male body storage of samples (or other differences) were responsible
odour, we were unable to replicate this on our main sample for the null effect of MHC dissimilarity.
of women, in which none were pill users and all were in It is also possible that the null effect might have been
the follicular cycle phase. We based the design of our study due to the inclusion of men who were assessed under
on that of Wedekind et al. (1995); like them, (i) we tested either the MHC-similar or MHC-dissimilar condition,
preferences among three MHC-similar and three MHC- but not in both. For example, it could have been that those
dissimilar odours, (ii) odours were captured on cotton included only as MHC-similar men had especially
t-shirts worn in bed, (iii) odour donors were asked to avoid attractive/weak odour, while those included only as
potentially confounding environmental odours, (iv) men- MHC-dissimilar men had very unattractive/intense
strual cycle stage was controlled and so on. odours. MHC studies should aspire to balance inclusion
However, there were nonetheless some methodological in either condition across the sample to avoid these
differences that could have accounted for the differences in non-MHC related effects ( Wedekind 2002). In our
the results. Wedekind et al.’s women used nasal sprays to study, logistical reasons led to 14 per cent of ratings
help their sense of smell, and read Süskind’s novel Das relating to men who contributed in only one condition.
Parfum to raise awareness of their smell perception. Ours However, we found no evidence for systematic
did neither of these, but these omissions are unlikely to be differences in odour pleasantness, desirability or inten-
critical since other studies that omitted these requirements sity, suggesting that this was unlikely to be responsible
for the null effect. Furthermore, the effect of excluding associate with MHC-similar females, presumably using
these men’s shirts from analyses was to reduce, rather odour (Manning et al. 1992), while females in oestrus
than enhance, the difference between mean similar and prefer odours of MHC-dissimilar males (and other aspects
mean dissimilar ratings. of genetic quality involved in mate choice, Roberts &
Our data provide further evidence that use of oral Gosling 2003). In our study, paired women expressed
contraceptives influence women’s MHC-correlated odour greater preferences for MHC dissimilarity in odours
preferences. The significant session–group interaction, of unfamiliar men, and there was a non-significant
whereby ratings shift in favour of MHC similarity after association between fantasizing about extra-pair relation-
initiating pill use, in contrast to the control group, is ships and MHC-dissimilar odour preference. Such
consistent with Wedekind et al.’s (1995) suggestion that expression of enhanced preference for dissimilarity might
pill use may disrupt adaptive mate preferences. Indeed, be interpreted within the context of desired attributes in
our results are the first to test this suggestion empirically. extra-pair partners as a means to increase offspring
The slight change in the control group of non pill-users heterozygosity, in common with similar preferences in
could arguably be interpreted in terms of increased birds (e.g. Petrie & Kempenaers 1998; Blomqvist et al.
experience in olfactory testing, eliciting a slightly stronger 2002), although it is curious that the effect was elicited
preference for MHC dissimilarity, but this was not most strongly in the long-term context question—perhaps
matched by the pill group. Although we had only one this question focuses raters more successfully on desired
woman in our pill-using group who used a POP, mate choice characteristics than does rating of odour
excluding her from analysis improved the explanatory pleasantness. It may also be that paired women can
power of desirability ratings on change in odour evaluate odours more accurately, and thus discriminate
preference. We could therefore speculate that POP use MHC dissimilarity more effectively, because they have
may have less influence on this change than the combined more intimate recent experience of male odour (although
pill, but this is based on only one woman and needs we do not know why single women should have preferred
further testing. MHC-similar men). Similarly, women in established
At least two alternative explanations for the difference partnerships express clearer or different preferences for
among Wedekind et al.’s (1995) groups of pill-using and traits indicating additive genetic variance than single
non-using women could be proposed. One is that the women, in both visual (Little et al. 2002) and olfactory
association between MHC-similarity preference and pill (Havlicek et al. 2005) modalities, but the extent to which
use is a by-product of increase in preference for MHC these discrepancies ultimately reflect underlying strategic
heterozygosity, since heterozygous men are on average variation or differences in experience remains a question
more likely to share alleles with women raters (cf. Roberts for further study.
et al. 2006) and Thornhill et al. (2003) report greater We do not know whether the change in preferences
preference for heterozygotes in the luteal phase. However, related to pill use is sufficiently strong to influence partner
our results indicated no difference in preferences for choice, but it could do so if odour plays a significant role in
heterozygotes in either non-users or pill-users. A second actual human mate choice. Some studies have suggested
possibility, one which stimulated this study, is that there that women consider the olfactory domain to be an
might be pre-existing behavioural differences between important factor in their assessment of potential partners
women who choose to use the pill and those who do not. (e.g. Havlicek et al. 2008). Although we were unable to
Indeed, we found that pill users used rating scales replicate the effect, Wedekind et al.’s (1995) demon-
differently, awarding higher scores, on average, than stration of an association between MHC dissimilarity and
non-users. Importantly, this difference was apparent the reminiscence of current or previous partners suggests
even before they initiated pill use, although we do not that the influence of MHC-odour cues may extend beyond
know the reason for this. While absolutely higher ratings the laboratory. If this is the case, our results indicate that
could not lead to the difference found by Wedekind et al., it use of the contraceptive pill could lead to choice of an
could potentially arise from a positive association between otherwise less preferred partner.
pill use and other attributes such as attractiveness or
The study design was approved by the Ethics Committee of
likelihood of being in a sexual relationship. We found no the Newcastle and North Tyneside NHS Trust.
evidence for an effect of attractiveness on preferences or
pill use, but we did find an association between This work was funded by the Wellcome Trust. We are grateful
relationship status and MHC preference. However, in to the staff at the National Blood Service Tissue Typing
direct contrast to what might be inferred from Wedekind Laboratory for their assistance, to Diana Mansour for her
et al.’s data, paired women showed higher preference for advice, to the Graingerville Contraception Clinic for help
with recruitment and three anonymous reviewers for
MHC dissimilarity while single women preferred MHC comments. Finally, we thank all our long-suffering volunteers
similarity. This intriguing effect of relationship status is for their participation.
discussed further below, but it is worth noting that it may
be at least partly responsible for the variability in findings
across MHC-odour studies.
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