Celebrities and TV stars like Caitlyn Jenner, Laverne Cox, Jazz Jennings and Chaz Bono have helped take what was once a taboo subject and turned it into part of America’s mainstream conversation. This long-overdue discussion helps foster broader understanding and acceptance, and it also shines a light on a largely underserved area of medical need. 

Rising Beyond a Difficult Legacy

Transgender patients have suffered from a lack of properly trained physicians and pharmacists, as well as general disrespect by the medical world that has failed to recognize transgenderism as a medical condition. This has herded many patients into a world of self-treatment and buying questionable hormone replacement from internet pharmacies. 

Over the last 15 years it has been ZRT’s privilege to work with doctors and their patients who are transitioning their physical body from one gender to another. Many times when we work with a clinician, we hear a story of a patient’s long struggle to get their external body to align with their inner identity. ZRT’s hormone testing allows the patient to monitor hormone levels while on hormone treatment, and our interpretation takes into account the patient’s symptoms as well as supplementation and where they are in their gender hormonal transition.

Learning a New Sets of Needs

Hormone supplementation for patients who are physically transitioning hormonally from one gender to another is different from other types of hormone replacement. For example, when we decide on hormone treatment with menopausal patients, we usually use low and physiological dosing. However, when we are helping transition a patient hormonally, we must use much higher dosages, although bio-identical hormone replacement therapy (BHRT) is still appropriate.

When patients wonder why the dosage is so different, the best analogy is puberty! We have to change tissues that have already changed once, as well as suppress the hormones that the body continually wants to produce. Suppressing endogenous production and replacing with exogenous hormones, all the while minimizing adverse effects of these hormones is a continual challenge in transgender individuals.  

Hormonal Influence in the Womb

Gender is an interesting embryological transition. By default, we are all outwardly female in the womb. Within the second and third months of gestation, the testicles of the male fetus secrete androgens which stimulate the growth of the phallus. Failure in the completion of the numerous origami folds of tissue can result in a variety of congenital abnormalities of the penis. The process is so complicated that it’s amazing anyone has normal genitalia.

The fetus’ adrenal androgens can also have an influence such as that seen in female babies with pseudo-hermaphrodism. In these cases, the baby’s adrenal glands produce large quantities of androgens, causing fusion of the labia majora that gives the appearance of a scrotum in female fetuses. In male pseudo-hermaphrodism, the adrenal hormones may be lacking, which causes a variety of phallus abnormalities.

In another rare syndrome, testicular feminization syndrome, the child is born with XY chromosomes but has external genitalia of female. The tissue is unresponsive to the androgens therefore the genitalia retain an overall female appearance; however, testicles are present and female genital structures, like the vagina, may be poorly developed. Women who have testicular feminization syndrome usually identify as women with less transgender trauma as their genitals also appear to be female.  

Today’s Leading Gender Development Theories

Throughout pregnancy, fetal hormones saturate not only the body of the developing fetus, but also the fetal brain. In addition, the fetus is exposed to any medications the mother is using, her own hormones, nutrients she consumes, and chemicals to which she is exposed. The male fetal brain has extremely high levels of testosterone at several time points throughout pregnancy and immediately postpartum. The first surge is approximately at 12-18 weeks, the second weeks 34-40, and the third time is the first 3 months after birth. Immediately postpartum, levels can be as high as an adult man, although most of the hormone is bound and not free. These surges in hormones appear to set the brain’s neurons upon a gendered path that may or may not reflect the body’s phenotypical gender which has formed weeks to months before. There is growing concern regarding the role of environmental toxins and xeno-hormones (e.g., Bisphenol A) in disrupting these intrauterine surges of hormones.

There are three main ideas on how hormones influence the brain.  The first theory suggests that when the pulses of testosterone from the fetal testes fail to occur, there is consequently no stimulation of nerve cells to grow in the “male direction.”  This is thought to mostly affect the bed nucleus of the stria terminalis (BSTc) of the limbic system although exactly which structures are involved is still questioned by some.  It is unlikely that gender identity is only seated in one section of the brain; instead it is likely that multiple sections of the brain inform us of our genders.  These hormonal signals cause the neurons to interact with other neurons in a gender specific way.

The second theory is that specific brain structure (e.g., Uncinate nucleus) fails to connect with other regions of the brain in a gender specific pattern. This is a much more complex view of gender brain development since multiple structures and neuronal patterns within the brain are involved. Thus, by looking at the brain structures of neural development you might “see” alterations in gender identity. In fact, we can see MRI changes in the size of different brain structures; however, not until adulthood are they obvious. Most transgender adults have feelings of gender dysphoria in early childhood, so we know that gender is established in-utero although the brain may be stimulated or triggered as late as puberty.

The third theory of transgenderism lies in the gene alteration that may or may not interact with hormone levels. In mice, 50 genes responsible for gender-specific brain morphology changes have been found to be expressed even in the absence of hormones. Thus, activation or failure to activate a gene may contribute to dysmorphic individuals.

What we do know about being transgender is that it is not how you are raised that determines your self-identity of gender. Children in the 1950s through the 1970s with congenital adrenal hyperplasia and pseudo-hermaphrodism who were born as a male gender, but raised female have taught us that the brain’s gender identity appears to be permanent and fixed at birth. Many of these children raised female returned to their male gender in adulthood but not until they’d experienced a lot of heartache.

I hope that this blog spurs our medical readers into learning more about how you can serve these patients in your communities. ZRT as always, is proud to help contribute to the health of ALL individuals seeking hormone balance.

Useful Resources

The World Professional Association for Transgender Health (https://www.wpath.org/)

National Health Service (UK) “Guide to Hormone Therapy for Trans People”: http://www.teni.ie/attachments/9ea50d6e-1148-4c26-be0d-9def980047db.PDF

Presentation by Nick Gorton, “Primary Care and Hormonal Treatment for Transgender Patients”: http://www.mghihp.edu/files/student-life/transgen-201.pdf

Swaab DF and Garcia-Falgueras A, “Sexual Differentiation of the Human Brain in Relation to Gender Identity”: http://www.functionalneurology.com/index.php?PAGE=articolo_dett&id_article=3373&ID_ISSUE=389