Berglund H, Lindstroem P, Dhejne-Helmy C, and Savic I. 2008. Male-to-female transsexuals show sex-atypical hypothalamus activation when smelling odorous steroids. Cerebral Cortex 18: 1900-1908.

The topic of olfactory loss-of-function in mammals spurred me to explore the current literature on human pheromone expression and reception, which we also discussed briefly on March 3^rd. My understanding of pheromones in old world primates is that there is no vomeronasal organ to receive and process these chemicals, and without an obvious pheromone sampling organ, it would be unlikely this method could be useful for signaling. Thus I was interested in the Berglund et al paper, which seemed to tackle two controversial topics—human pheromones and altered sex differentiation in the brain as either a result or cause of transsexuality. The article began by defining inclusion into the study group (nonhomosexual male-to-female transsexuals, who are described in the DSM as desiring long term acceptance as a member of the opposite sex, and bearing no known abnormal male phenotype or genotype) and introducing two steroids as potential human pheromones. These steroids, AND (present in male secretions such as saliva, semen, and sweat) and EST (found in the urine of pregnant women, but otherwise less well-studied overall) were shown in previous studies from 2006 and 2007 to differentially activate areas of the brain all associated with olfaction, mood, arousal, and sex drive depending on whether the receiver was male or female (AND: hypothalamus in women, amygdala and piriform cortex in men; EST: the reverse). In this study, researchers were interested in the pattern of brain activation acquired from physiologically male but socially female individuals.

The study focused on twelve male-to-female transsexuals (MTFRs) that were screened for hormone use, neurological damage, psychiatric disorders, sexual partners/attractions (all stated attraction to females, which I thought might be difficult to regulate), and onset of gender dysphoria (early in all cases). The subjects were required to passively smell high purity samples of AND, EST, and “OO” scents—lavender, cedar oil, eugenol, and butanol (this term wasn’t defined, but I took it to mean they were different, non-pheromone terpenoid type chemicals). MRI and PET scans were performed on each individual during smell tests following which the subjects were presented with the scent again and asked to rate its pleasantness, irritability, intensity, and familiarity. Scan outputs were analyzed with a color scale and activation clusters were measured in cubed centimeters. These steps were repeated with heterosexual male and female “controls,” and planned contrasts of pattern of activation between MTFRs and the control groups were tested with ANOVA adjusted for Bonferroni correction.

When using plain air as a reference, results indicated that hypothalamic activation did indeed differ between heterosexual male controls and MTFRs when smelling AND. Heterosexual men and women also differed—but only in the hypothalamic activations. In contrast, no significant differences were found between MTFRs and heterosexual women smelling EST. The kicker here was that MTFRs had hypothalamic activations in common with women smelling AND, but also slightly with men smelling EST, although more of the activation was seen in the piriform cortex and amygdala. Thus the MFTR sex-based response for potential pheromones seems somewhere between heterosexual males and females, but overall predominantly female.

Aside from suggesting that something about the hypothalamus seems to be regulated by response to pheromones or perceived sex, I was surprised that the steroid compounds were able to elicit a measurable response in parts of the brain other than the olfactory bulbs. However, this sort of paper must continue to call such steroids “candidate pheromones” because there doesn’t seem to be any way to observe or quantify information we receive (unconsciously?) from intraspecific chemicals. As I recall, the role of a receiver in communication is the most difficult to study because of this problem of quantification—but perhaps Berglund et al, with their unconventional topic, will be able to observe behavioral change in humans using these potential pheromones.