By Ara Y
Understanding Adult Trans Feminine Hormone Therapy
Disclaimer: Before we begin, It is important to understand that not all transgender people want to go through Gender Affirming Hormone Therapy (GAHT) also known as Hormone Replacement Therapy (HRT) and that is. Some transgender people may prefer to only socially transition or opt for certain surgeries. It is entirely based on the choice of the individual, and your transgender experience is valid, regardless of what you decide on.
It can be exciting to start GAHT and to have your gender affirmed physically, but it is equally important to be aware of what GAHT consists of, such as the types of medicines, the effects, long term preventative care and most importantly, the risks. This article covers the gist of it, but we recommend doing more intensive research which you can start by referring to the ‘further reading’ portion of this guide.
Let’s begin with understanding the sex hormones.
The Primary Sex Hormones
There are 2 to take note of:
| Testosterone (an androgen) (Sometimes known as T in the trans community) | Primary sex hormone in developing male sexual characteristics. |
| Estrogen (Sometimes known as E in the trans community): | Primary sex hormone in developing female sexual characteristics. |
| Bonus: Progesterone(Sometimes known as P in the trans community) | A progestogen sex hormone that has a number of physiological effects that are amplified in the presence of estrogens |
To simplify it, the goal of GAHT for a trans feminine person is to make estrogen the new primary sex hormone. You do this by reducing T so that it is no longer the primary hormone in your body, while increasing estrogen circulation.
It is important to note that though as a trans feminine person, your immediate knee jerk reaction might be to remove T in its “entire-T” (sorry!). But T provides both physiological (bone density, cardiovascular related) and mood related benefits (libido, mental health related), to human bodies of all sexes. Hence, the goal is to ensure levels are low enough to not be the primary sex hormone, but still high enough to retain the benefits. T should never be at 0.
In regards to progesterone, anecdotally, it is shown to aid in breast development (specifically at later growth stages, also known as tanner stages 4 and 5), and may provide other physiological benefits, such as skin health, libido and reducing the risk of blood clots.
It is often assumed that progestin and progesterone are interchangeable because they sound the same, but they are not. Progestin is a synthetic form of progesterone and though it may provide similar benefits, it actually increases the risk of breast cancer and can negatively impact cardiovascular health. However, due to the lack of data in current studies, the jury is still out on how vital progesterone is in the hormonal feminising process. So we’ll put that aside.
Blood Tests
Before we proceed to medication, let’s talk about the importance of blood tests. A blood test is the most definitive way of finding out if a hormone regimen is working for you, and if it is working safely based on your individual risk profile, pre-existing medical conditions, and medical history.
This table outlines the recommended blood work for monitoring feminising hormone therapy
Source: Rainbow Ontario’s Guidelines for Gender-Affirming Primary Care (2019)
Definitions:
CBC (Complete Blood Count),
ALT (Alanine transaminase, Liver Risk),
Creatinine (Kidney Risk),
Hba1c (Diabetes Risk),
Lipid Profile (Cholesterol, Cardiovascular Risk),
Total Testosterone(Free testosterone and testosterone that’s attached to proteins),
Estradiol (Most dominant form of estrogen in the body),
Prolactin (Risk of Prolactinoma with AA use).
The Medications
Antiandrogens
So how do we reduce T? Well, there are drugs called antiandrogens that block the effects of androgens (like T) in the body.
Steroidal antiandrogens such as Spironolactone and Cyproterone Acetate, work by lowering total testosterone in the body, while nonsteroidal antiandrogens, like Bicalutamide, work by blocking androgen receptors so your body doesn’t absorb T.
Bicalutamide, despite being a lesser-known antiandrogen, is slowly gaining traction – for a good reason, too. Studies show that it is more potent and efficient, while also being safer and more readily accepted compared to other nonsteroidal and steroidal antiandrogens, and should be prioritised in a regimen unless monotherapy is used (explained below).
Estrogen
We have learned about E, the hormone, now let’s talk about E as a medication. There are 2 important criterias to be aware of when administering E; its route of administration and the type of E being administered.
There are 2 distinct types: bioidentical and synthetic. A bioidentical drug is chemically identical to what your body would produce and comes from natural sources, such as plants, while the synthetic variant is man-made from chemical compounds. Bioidentical hormones cannot be considered “natural” though, as they’re also made in a lab. That being said, there are studies to show that bioidentical hormones are superior in terms of higher efficacy and are lower risk and should always be prioritised over synthetic hormones. Examples of bioidentical hormones are estradiol benzoate, estradiol valerate, estradiol cypionate and estradiol enanthate.
How can you tell the difference? While we can’t go through every type of medication, there’s an easy way to do it. Google the ingredients on the packaging along with the word “bioidentical”.
The next criteria is the route of administration. There are many routes of administration, but these are the more common ones used for GAHT:
| Oral administration | taken as a pill and swallowed |
| Sublingual administration | taken as a pill, placed under the tongue until absorbed |
| Transdermal administration | delivered through the skin via patches, creams or gels |
| Subcutaneous and Intramuscular Injections | injected into the body via fat(subcutaneous) or muscle(intramuscular) |
Deciding on whether to go with bioidentical or synthetic as well as the route of administration carries wildly different risks and benefits.
Understanding GAHT Risks
GAHT will be a long term medication regimen for a majority of trans individuals. Even if you are gender diverse and would only like to get some of the changes in sexual characteristics, you will be on GAHT for at least a couple of months.
It is very important to understand the medication you will be taking and the risks associated with it. High risks include Deep Vein Thrombosis (DVT), and some regimens work around it. Unfortunately, we are not able to explain in great detail all of the risks of each medication but have provided further reading below.
Common GAHT regimens
These are some GAHT regimens. Some are more commonly used than others for a variety of reasons including convenience, price point, accessibility of certain medications, a lack of experienced doctors, individual risk profile, and efficacy.
Assuming that all drugs used are bioidentical, the regimens are separated by rank of efficacy as well as by risk profiles. This is, of course, a generalisation, but it will give you a grasp of what to expect and help you in deciding which regimen to pursue.
NOTE: It is important to read the preparation before starting GAHT section if you do not have access to an endocrinologist.
| Medication | Relative Efficacy | Relative Risk Profile |
| Oral Estrogens + Antiandrogens | Low* | High^ |
| Sublingual Estrogens + Antiandrogens | Medium | Medium |
| Transdermal Estrogens + Antiandrogens | Medium – High | Low |
| Monotherapy: Transdermal Estrogen | Medium – High | Low |
| Monotherapy: Intramuscular or Subcutaneous Injections | High | Low |
^risk of blood clots and cardiovascular issues
*in regards to bioavailability of estradiol in serum blood levels
*Estrogen Monotherapy
Estrogen monotherapy is using estrogen on its own, without any antiandrogens. E alone is actually capable of reducing testosterone naturally, but a higher dose of E is required. This is why monotherapy is only recommended if bioidentical estrogens are used and if it is administered via the safest routes of transdermal and injection.
Timeline of Expected Changes
| Effect | Onset | Maximum |
| Redistribution of body fat | 3–6 mo | 2–3 y |
| Decrease in muscle mass and strength | 3–6 mo | 1–2 y |
| Softening of skin/decreased oiliness | 3–6 mo | Unknown |
| Decreased sexual desire | 1–3 mo | 3–6 mo |
| Decreased spontaneous erections | 1–3 mo | 3–6 mo |
| Male sexual dysfunction^ | Variable | Variable |
| Breast growth* | 3–6 mo | 2–3 y |
| Decreased testicular volume | 3–6 mo | 2–3 y |
| Decreased sperm production | Unknown | >3 y |
| Decreased terminal hair growth | 6–12 mo | >3 y |
Adapted from: The Endocrine Treatment of Gender Dysphoric/
Gender Incongruent Persons: An Endocrine Society Guideline & APTN’s Trans Feminine Resource Pamphlet
*changes are permanent
^reversible for some
There are a few expectations to set in regards to hair, voice, and body changes. Although facial and body hair can be reduced, it won’t be completely removed. Additional procedures such as electrolysis will be required.
Unfortunately, unlike our trans brothers on T, GAHT for trans feminine persons will not change your voice. You can seek the aid of a vocal coach, or go through voice training. GAHT will also have no effect on bone structure.
Conclusion
Check out the further reading portion below as there is always more to learn. Please also check out the preparation before starting GAHT resource, which is especially important if you don’t have access to a trans friendly and experienced endocrinologist.
Further Reading
Another reminder that understanding GAHT is just one part of the trans experience, so check out APTN’s other resources such as the SOGIESC guide or how to come out to others about your gender identity
APTN’s Trans Feminine Resource Pamphlet – Have a look at the Frequently Asked Questions!
Wikipedia – A shorter simpler guide compared to the other recommendations with reliable sources.
Rainbow Ontario – has excellent guidelines on risk management and long term preventative care.
WPATH8 – Standard of practice; a lot of doctors will strictly rely on this as a guideline though it is looked at by some endocrinologists to be conservative in terms of best practices.
CITATION:
1; National Library of Medicine. Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis. Noor Asi, Khaled Mohammed et al. 26 July 2016.
2;