The following is a letter I sent to an editor of the International Journal of Transgenderism:
http://www.symposion.com/ijt/

Dr. Coleman,

Hello, my name is Lynn. I came across your name on the International Journal of Transgenderism as an editor for that publication. I am a 30 year old pre-operative transsexual in the St. Louis area, and have been reading about the possible cause of transsexuality for quite some time.

In 1991, Dr. Sarah Seton speculated a connection between the aromatase enzyme and transsexuality in her paper ‘An Open Letter to Physicians’ (1). Since finding this article, I have spent time reading on the effect of aromatase. This morning I found the article entitled ‘A Sex Difference in the Human Brain and its Relation to Transsexuality’, published in the IJ, and again mentioning a section of the brain which is sexually dimorphic and a site of aromatization (2).

The CYP19 (aromatase) section of DNA has been isolated, and been found to have tissue-specific transcripts. (3)

‘The gene encoding human aromatase has been cloned and characterized and shown to be unusual compared to genes encoding other P450 enzymes, because there are numerous untranslated first exons that occur in aromatase transcripts in a tissue-specific fashion due to differential splicing as a consequence of the use of tissue-specific promoters. Thus, expression in the ovary uses a proximal promoter that is regulated primarily by cAMP. On the other hand, expression in the placenta uses a distal promoter located at least 40 kb upstream of the start of transcription that is regulated by retinoids. Other promoters are used in brain and adipose tissue. In the latter case, class I cytokines such as IL-6 and IL-11, as well as TNF-à, are important regulatory factors. A common 3'-splice junction located upstream of the start of translation is used in all of the splicing events involved in the use of these various promoters. Thus, the coding region of the transcripts, and hence the protein, are identical regardless of the tissue site of expression; what differs in a tissue-specific fashion is the 5'-end of the transcripts. This pattern of expression has great significance both from a phylogenetic and ontogenetic standpoint’

As for myself, I had severe depression before beginning an SSRI prior to transition, which not only corrected the depression, but also problems I had where my body didn’t sweat properly, and social anxiety. These pointed to a lack of available seretonin, which could be caused by a deficiency in aromatase. After starting hormone replacement therapy, I was switched from 30mg of Paxil to 20mg of Celexa, and have since decreased to 10mg a day. The previous symptoms have not returned, in the presence of estrogen. I will eventually be completely taken off of SSRIs and believe the symptoms still won’t return.

When you consider gender identity dysphoria (presumably from female brain morphology) along with the fact that all the functions I had problems with are handled by aromatizing portions of the brain (hypothalamus, amygdala, and hippocampus), this all seems to point to a damaged portion of the CYP19 gene in DNA. Has anyone at the International Journal of Transgenderism considered testing such things? Damage to DNA is something that all transsexuals could be screened for. Unlike looking for aromatase deficiency itself, DNA damage does not require autopsy.

As I said before, I’m not a doctor, or medical student. I’m a person suffering from gender identity dysphoria, and in the midst of gender reassignment. The impact of positive proof of the cause of transsexuality could move it from being a psychological condition (listed in the DSM) to being a medical condition. This could also make legal issues of transition easier to accomplish. Most importantly though, it would answer the persistent nagging question of ‘why’ for me.

If there is ever any study done in this, I would be more than happy to assist by giving a blood sample for DNA testing. I’m sure virtually every M-t-F TS I know would be equally willing.

I don’t know if anyone else has ever considered this, being that the human genome project was only recently finished. I also don’t know who else to approach with this information. I hope that you can act upon this information, or pass it along to someone who may.

Thank you for your time and attention in this matter.

Sincerely,
Lynn
 

References can be found at:
1). http://www.genderweb.org/medical/docs/gmed19.html
2). http://www.symposion.com/ijt/ijtc0106.htm
3). http://www.faseb.org/fj/jan97/simpson.html

Other information gathered at:
http://www.le.ac.uk/cmht/der2/abstracts.html
http://www.karger.ch/journals/nen/nen663/nen0173.htm
http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?107910#ALLELIC_VARIANTS
http://journals.endocrinology.org/joe/150/joe150s051.htm