Informational Resource for Transgender and Gender Diverse Adolescents and Their Families – Adolescent Gender Affirming Estrogen

Information About Estrogen

NOTE: This information is compiled from several sources readily available on the internet as identified below. When considering gender-affirming medications, it is important to learn about the risks, expectations, and long-term considerations associated with transition to more estrogen/progesterone in the body

DISCLAIMER: The information contained herein is for informational purposes only and is not intended to substitute for medical advice or constitute medical advice. The information contained herein does not create a health care provider-patient relationship between the reader and any of the authors. The information contained herein is not intended to be definitive or exhaustive, and is compiled from sources believed to be accurate, but the authors make no representation that it is accurate. Moreover, the authors and their agents make no warranties or guarantees, express or implied, concerning the accuracy or appropriateness of this information for any particular reader given the frequent changes in the practice of medicine as new information is learned through medical studies. Readers should consult with a knowledgable healthcare provider for medical advice, treatment, and additional information on gender affirming care options based on their specific health care needs and medical history. For more information on potential risks, expectations and other long term considerations, please consult “WPATHSOC8, S43 - S79,”Standards of Care for Health of Transgender and Gender Diverse People, Version 8, by E. Coleman, et al., available at: https://www.tandfonline.com/doi/pdf/10.1080/26895269.2022.2100644.[1]

All About Estrogen And Progesterone

It is very important to remember that everyone is different, and that the extent someone's body may change and how quickly those changes happens will depend on many factors. These factors include genetics, the age at which a person starts taking hormones, and a person's overall state of health.

It is also important to remember that because everyone is different, one person's medicines or dosages may be different from those of their friends, or what they read in books or online. Many people are eager for changes to take place rapidly and believe taking more medication will make changes occur faster; this is not necessarily true. Please remember that starting gender affirming hormone therapy is going through a puberty, and puberty normally takes several years for the full effects to be seen. Taking higher doses of hormones will not necessarily make things move more quickly — it may, however, endanger one's health.

(Seattle Children’s Gender Clinic, “A Guide to Gender Affirming Hormone Therapy with Estrogen”)

What are estrogen and progesterone?

Estrogen and progesterone are sex steroid hormones that are made in abundance by ovaries. Ovaries and bodies with ovaries make 3 highly functional forms of estrogen (E1, E2, E3) and 10–15 minor forms of estrogen. They also make 1 highly functional form of progesterone (P4) and about 9 minor forms. Hormones tell the cells what to do, which changes a person's body and brain.

(Cleveland Clinic, “Estrogen”; The Endocrine Society, “What Does Estrogen Do?”; UCSF “Overview of feminizing hormone therapy”; Seattle Children’s Gender Clinic, “A Guide to Gender Affirming Hormone Therapy with Estrogen”)

What do these hormones do?

Estradiol (E2) is the hormone responsible for softer skin and curvier body shapes. It causes the physical changes of transition, as well as many of the emotional changes. Progesterone has a number of reported benefits, such as improved mood, energy, and libido, better breast development, and better body fat redistribution or “curves”. There is very little scientific evidence to support these claims. However, some people do prefer to take progesterone and report some of these benefits.

Physical Changes From Hormone Therapy:

Skin

The first changes a person typically notices is that their skin will become a bit drier and thinner. Pores will become smaller, and there will be less oil production. One may become more prone to bruising or cuts. People may notice that they perceive pain or temperature differently, or that things just “feel different” when they touch them. Skin changes are usually noticed within a few weeks. In these first few weeks a person will notice that the odors of their sweat and urine will change, and that they may sweat less overall.

Breasts

Within the first few weeks of starting treatment, most people notice small “buds” developing beneath their nipples. These may be slightly painful (especially to the touch) and uneven between the right and left side. This is part of the expected course of breast development. The pain will diminish somewhat over the course of several months. Breast development is quite variable from person to person. Not everyone develops at the same rate, and most people can expect to develop breasts based on their pre-existing genetics and the number of years their body made testosterone in higher amounts. Like the breasts of cis women, the breasts of all people vary in shape and size and are sometimes different sizes or shapes between the right and the left.

Weight

Weight will begin to redistribute around the body. Fat will begin to collect around hips and thighs, and the fat under a person's skin throughout their body will become a bit thicker, giving arms and legs less muscle definition and a smoother appearance. Hormones will not have a significant effect on the fat in a person's abdomen. Muscle mass will decrease, as will strength (a person starting hormone therapy should continue to exercise to maintain muscle tone as well and general health). Depending on your, lifestyle, genetics, and starting weight and muscle mass, a person may gain or lose weight once they begin hormone therapy.

The fat under the skin in the face will increase and shift around to give the eyes and face in general a softer, fuller appearance. Please note that bone structure (including your hips, arms, hands, legs, and feet) will not change if a person has completed their endogenous (or first) puberty. The facial changes can take up to two or more years to see the final result; it is usually a good idea to wait at least two years after beginning hormone therapy before considering any gender affirming[3][4][5][6]surgical facial procedures.

Hair

Facial hair, as well body hair (hair on the chest, back, legs, and arms) will often decrease in thickness and may grow at a slower rate. However, it usually doesn’t all go away, and most people need electrolysis or laser removal to help reduce unwanted hair. If someone has had any scalp balding, this should slow or stop, though the amount that will grow back for each person varies.

Emotional Changes:

Overall emotional state may or may not change, and changes vary from person to person. Puberty is a roller coaster of emotions and a second puberty experienced during transition is no exception. Some people find that they have access to a wider range of emotions and feelings or have different interests, tastes, or pastimes. Some people find they behave differently in relationships with other people. While mental health counseling is not for everyone, most people would benefit from a course of supportive mental health counseling while in transition to help explore these new thoughts and feelings and get to know their new self. Most studies show a significant improvement in overall well-being after gender affirming hormone therapy has begun. This is most likely due to better alignment of the physical body with the psychological gender identity.

Sexuality:

Soon after beginning testosterone suppression and treatment with estrogen, most people with penises notice a decrease in the number of erections that they have, and generally those erections that do occur are less firm and do not last as long. Some people lose the ability to penetrate with their penises. Most people still have sexual sensation and are still able to orgasm, although these orgasms may be “dry” (they might not produce ejaculate). Sex may feel different, with potentially different body parts or different sex acts contributing to erotic pleasure. Many people find that orgasms will feel different, possibly with more of a “whole body” experience, less peak intensity, and longer duration. It can be very helpful to explore and experiment with changes in sexuality through masturbation, using sex toys[7](remember to clean and sterilize between uses), and involving your sexual partner(s).

Typically testicles will shrink to half of their original size or less. In nearly all cases, this does not affect the amount of scrotal skin available for future genital surgery, if those treatments are desired.

Reproduction/ Fertility

Anyone starting estrogen and/or progesterone therapy must assume that within a few months of beginning hormone therapy, they will become permanently and irreversibly sterile. While some people may be able to maintain a sperm count on hormone therapy, or have their sperm count return after stopping hormone therapy, it is impossible to know who will or will not regain fertility. Anyone who thinks that there is any chance that in the future they might want to produce a child using their own sperm should speak to a doctor about preserving their sperm in a sperm bank. This process generally takes 2–4 weeks and is rarely covered by health insurance. Sperm storage should be completed before beginning any hormone therapy. Although many people are able to stop hormones and go on to make biological children, there is simply no way to know if that will be true for a particular individual.

Because of this unpredictability, if a person is on hormones and having penetrative vaginal sex with someone who is able to become pregnant, they should always use a reliable birth control method to prevent unwanted pregnancy.

(Physical changes have been compiled from UCSF “Overview of feminizing hormone therapy”, Seattle Children’s Gender Clinic, “A Guide to Gender Affirming Hormone Therapy with Estrogen, and Fenway Health, “Medical Care of Gender Diverse Children and Adolescents.”)

Are these changes reversible?

Many of the effects of hormone therapy are reversible if someone stops taking hormones. The degree to which effects are reversed depends on how long they have been taking hormones and how far they went through their endogenous puberty. Breast growth, and possibly sterility, are not reversible.

Hormones after surgery

People who have had an orchiectomy (removal of the testicles) or genital reassignment surgery will probably be able to take a lower dose of hormones and may not need additional medicines that block testosterone. However, it is important to remain on some hormones post-operatively, until at least age 50 years old and possibly older; this helps prevent a weakening of the bones, known as osteoporosis.

What are the risks of hormone therapy?

Risks associated with estrogen and progesterone hormone therapy include high blood pressure, blood clots, liver problems, stroke, and perhaps diabetes. Because there are not many long-term studies on the use of estrogen in people, there are potential unknown risks. It‘s possible that in the future we’ll learn about more risks or side effects, particularly when estrogen is used for many years. Contrary to what some people believe, a very small amount of estrogen is needed to deliver the maximum effect. Taking very high doses of estrogen does not make changes happen more quickly, and it can be dangerous and harmful to one's health.

There is not much scientific evidence about the risks of cancer in people taking gender affirming hormone therapy. We believe that your risk of prostate cancer will go down, but since we are not sure, you will still need follow guidelines and medical advice for testing for that cancer when appropriate. Your risk of breast cancer will increase. Breast cancer screening with mammograms is recommended to begin between ages 40 and 50, for people who have been on hormones for more than 5 years. (UCSF “Overview of feminizing hormone therapy”, Seattle Children’s Gender Clinic, “A Guide to Gender Affirming Hormone Therapy with Estrogen, and Fenway Health, “Medical Care of Gender Diverse Children and Adolescents.”)

What forms do these medications come in?

Hormone therapy may include estrogen and progesterone. Estrogen is taken as estradiol and may be given as a pill, by injection, or by several preparations applied to the skin, such as creams, gels, sprays or patches. Progesterone is taken as micronized progesterone, in a capsule or cream form. Puberty blocking and testosterone blocking medicine is covered here[8]. (Fenway Health, “Hormone Options: Estrogen Therapy”)

What and how to take it?

All of the information below is compiled from Seattle Children’s Gender Clinic “Gender-Affirming Hormone Protocols” and Fenway Health’s “Medical Care of Gender Diverse Children and Adolescents.”

The information has been collected to create a comprehensive guide for patients (and health care providers less familiar with these treatment regimens), but is NOT intended to be a substitute for medical advice from a doctor or other health care professional familiar with your particular case and medical history. Please take these medication as directed by your doctor.

You can always start on a lower dose and increase as you feel ready. In fact, that is usually recommended.

Estradiol forms:

Pills — come in 0.5mg, 1mg, and 2mg tablets, and are taken every day by swallowing or dissolving under the tongue.
- Starting doses
  - Early adolescence (age 9–12): 0.25mg–0.5mg
  - Middle adolescence (age 13–15): 0.5mg–1mg
  - Late adolescence (age 15+): 1mg–2mg
- Dose increases
  - Early adolescence (age 9–12): 0.25mg–0.5mg every 6 months
  - Middle adolescence (age 13–15): 0.5mg–1mg every 3–6 months
  - Late adolescence (age 15+): 1–2mg every 3 months
- Most adults take between 4 and 8mg of estradiol each day. Once your dose requires that you add a second tablet, take the tablets about 12 hours apart (so once in the morning and once in the evening).

Patches — come in 25mcg, 50mcg, and 100mcg and are placed on the skin once or twice a week.
- Starting doses
  - Early adolescence (age 9–12): 6.25–12.5mcg (1/4–1/2 of 25mcg patch)
  - Middle adolescence (age 13–15): 25mcg patch
  - Late adolescence (age 15+): 25mcg-37.5mcg patch
- Dose increases
  - Early adolescence (age 9–12): 6.25–12.5 mcg (1/4 – 1/2 of 25 mcg patch) every 6 months
  - Middle adolescence (age 13-15): 12.5–25mcg every 3–6 months
  - Late adolescence (age 15+): 25–50mcg every 3 months
- Most adults use between 200 and 400mcg patches. Patches are either replaced once or twice a week depending on the brand. It is okay to use more than 1 patch to make your total dose. You may need to use additional bandages with adhesive or tape to get the patches to stick.
Injections
- Estradiol cypionate 5mg/mL is injected subcutaneously (under the skin) or intramuscularly (into the muscle) once a week.
  - Starting doses
    - Early adolescence (age 9–12): 0.5mg (0.1mL)
    - Middle adolescence (age 13–15): 0.5-1mg (0.1–0.2mL)
    - Late adolescence (age 15+): 1.5mg (0.3mL)
  - Dose increases
    - Early adolescence (age 9–12): 0.5mg (0.1mL) every 6 months
    - Middle adolescence (age 13–15): 0.5–1mg (0.1–0.2mL) every 3–6 months
    - Late adolescence (15+): 1mg (0.2mL) every 3 months
  - Most adults take around 0.75mL to 1.2 mL once a week.
- Estradiol valerate 10mg/mL, 20mg/mL, or 40mg/mL are used less commonly in younger patients because it tends to cause elevated estradiol levels. If you are going to use it, it is best to use the 10mg/mL strength. You can use the same mg (dose) as estradiol cypionate above, but the mL (volume) will be half of the above. You often need to split the dose of estradiol valerate in half and inject it twice a week to avoid big dips in your mood a day or two before injecting.

Progesterone forms:

Capsules — come in 100mg or 200mg, are taken daily, and can be swallowed before bedtime.
- Starting doses
  - Early adolescence (age 9–12): NONE, wait for 6–12 months of estrogen therapy before starting.
  - Middle adolescence (age 13–15): 100mg
  - Late adolescence (age 15+): 100mg
- Dose increases
  - Early adolescence (age 9–12): None
  - Middle adolescence age (13–15): 100mg every 6-9 months
  - Late adolescence (age 15+): 100mg every 3–6 months
- Most adults take about 200mg of progesterone a day. The most they take is 400mg a day.
Creams — can be ordered from compounding pharmacies. 25mg of cream works as well as a 100mg capsule.

WARNING: Taking more hormones will not make your changes progress more quickly and can be unsafe. It is important to be patient and remember that this puberty can take years to develop all of its changes — giving it more time might actually result in more or better changes overall.

References

E. Coleman, A. E. Radix, W. P. Bouman, G. R. Brown, A. L. C. de Vries, M. B. Deutsch, R. Ettner, L. Fraser, M. Goodman, J. Green, A. B. Hancock, T. W. Johnson, D. H. Karasic, G. A. Knudson, S. F. Leibowitz, H. F. L. Meyer-Bahlburg, S. J. Monstrey, J. Motmans, L. Nahata, T. O. Nieder, S. L. Reisner, C. Richards, L. S. Schechter, V. Tangpricha, A. C. Tishelman, M. A. A. Van Trotsenburg, S. Winter, K. Ducheny, N. J. Adams, T. M. Adrián, L. R. Allen, D. Azul, H. Bagga, K. Başar, D. S. Bathory, J. J. Belinky, D. R. Berg, J. U. Berli, R. O. Bluebond-Langner, M.-B. Bouman, M. L. Bowers, P. J. Brassard, J. Byrne, L. Capitán, C. J. Cargill, J. M. Carswell, S. C. Chang, G. Chelvakumar, T. Corneil, K. B. Dalke, G. De Cuypere, E. de Vries, M. Den Heijer, A. H. Devor, C. Dhejne, A. D’Marco, E. K. Edmiston, L. Edwards-Leeper, R. Ehrbar, D. Ehrensaft, J. Eisfeld, E. Elaut, L. Erickson-Schroth, J. L. Feldman, A. D. Fisher, M. M. Garcia, L. Gijs, S. E. Green, B. P. Hall, T. L. D. Hardy, M. S. Irwig, L. A. Jacobs, A. C. Janssen, K. Johnson, D. T. Klink, B. P. C. Kreukels, L. E. Kuper, E. J. Kvach, M. A. Malouf, R. Massey, T. Mazur, C. McLachlan, S. D. Morrison, S. W. Mosser, P. M. Neira, U. Nygren, J. M. Oates, J. Obedin-Maliver, G. Pagkalos, J. Patton, N. Phanuphak, K. Rachlin, T. Reed, G. N. Rider, J. Ristori, S. Robbins-Cherry, S. A. Roberts, K. A. Rodriguez-Wallberg, S. M. Rosenthal, K. Sabir, J. D. Safer, A. I. Scheim, L. J. Seal, T. J. Sehoole, K. Spencer, C. St. Amand, T. D. Steensma, J. F. Strang, G. B. Taylor, K. Tilleman, G. G. T’Sjoen, L. N. Vala, N. M. Van Mello, J. F. Veale, J. A. Vencill, B. Vincent, L. M. Wesp, M. A. West & J. Arcelus (2022) Standards of Care for the Health of Transgender and Gender Diverse People, Version 8, International Journal of Transgender Health, 23:sup1, S1-S259, DOI: 10.1080/26895269.2022.2100644. https://doi.org/10.1080/26895269.2022.2100644
Wylie C Hembree, Peggy T Cohen-Kettenis, Louis Gooren, Sabine E Hannema, Walter J Meyer, M Hassan Murad, Stephen M Rosenthal, Joshua D Safer, Vin Tangpricha, Guy G T’Sjoen, Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 102, Issue 11, 1 November 2017, Pages 3869–3903, https://doi.org/10.1210/jc.2017-01658
Thompson, J, Cavanaugh, T, Hopwood, RA, & Vetters, R. Protocol for the Gender Affirming Care of Transgender, Non-binary, and Gender Diverse Children and Adolescents. April 2019. Fenway Health, Boston. https://fenwayhealth.org/wp-content/uploads/Medical-Care-of-Gender-Diverse-Children-Fenway-Health-Spring-2019-1.pdf
Seattle Children's. (2023, June). Seattle Children’s Gender Clinic Gender-Affirming Hormone Protocols. https://www.seattlechildrens.org/globalassets/documents/clinics/gender/scgc-gah-protocols.pdf