The Different Types of Estrogen Treatment for Transfeminine People (2024)

Transgender women and transfeminine people are persons who were assigned male at birth, yet identify as women or as having a gender identity that is predominantly feminine. Transgender or trans people represent a group that includes not just transgender women but also non-binary people who have a more feminine gender identity than the one that is expected for their recorded sex at birth.

The term "transfeminine" is an umbrella term that encompasses both transgender women and feminine people of nonbinary identity. Many transgender people experience what is known as gender dysphoria—this is discomfort caused by people's bodies not matching their sense of identity.

Not every transgender person deals with their gender dysphoria in the same way. However, for many people, hormone therapy can help them feel more like themselves. For transmasculine people, this involves testosterone treatment. Testosterone is a type of androgen (male sex hormone). For transfeminine people, this usually involves a combination of androgen blockers (also known as testosterone blockers) and estrogen treatment.

Effects of Estrogen Treatment

Androgen blockers are a necessary part of estrogen treatment for transfeminine people because testosterone acts more strongly in the body than estrogen does. Therefore, in order for transfeminine people to experience the effects of estrogen treatment, they must block their testosterone. The most common medication used to block testosterone is spironolactone or "spiro."

Some also have their testicl*s removed (orchiectomy) so that they can take a lower dose of estrogen and not need an androgen blocker. This is because testosterone is primarily produced in the testicl*s.

The purpose of estrogen treatment for transfeminine people is to cause physical changes that make the body more feminine. The combination of an androgen blocker with estrogen can lead to the following types of desired changes in the body:

• Breast growth
• Decreased body and facial hair
• Decreased muscle mass
• Redistribution of body fat
• Softening and smoothing of the skin
• Reduced acne
• Slowed and possible reversal of scalp balding

All of these are changes that can reduce gender dysphoria and improve quality of life. There are also some changes that occur that are less obvious. Some of these, like a reduction in testosterone, fewer penile erections, and a decline in blood pressure are generally considered to be positive changes. Others, like decreased sex drive and changes in cholesterol and other cardiovascular factors, may be less desirable.

The physical changes associated with estrogen treatment may start within a few months. However, changes can take two to three years to be fully realized. This is particularly true for breast growth. As many as two-thirds of transgender women and transfeminine people are not satisfied with breast growth and may seek breast augmentation. Research suggests that this procedure depends on a number of factors including when hormone treatment is started and how fully testosterone is suppressed.

Methods for Taking Estrogen

When used for gender-affirming care, estrogen is available in different formulations:

• Oral pill (taken by mouth and swallowed)
• Sublingual tablet (dissolved under the tongue)
• Intramuscular injection (injected into a large muscle)
• Subcutaneous injection (injected under the skin)
• Transdermal patch (delivered through the skin in an adhesive patch)
  

The choice of estrogen is not just a matter of preference. Different forms of estrogen are absorbed and distributed throughout the body differently—some more efficiently and less problematically than others.

Oral estrogen is one such example.

When many oral drugs are swallowed, they are taken directly to the liver to be metabolized (broken down) before being released in general circulation to exert their intended action.

The problem with estrogen is that the liver is very effective in removing much of the active hormone from circulation. This is known as the "first-pass effect" in which liver metabolization reduces the concentration of circulating drug.

As a result, you need to take higher doses of oral estrogen, sometimes 10 to 20 times higher, in order for there to be enough active estrogen in the body. At this dose, estrogen can cause complications, like high triglycerides, gallstones, and an increased risk of heart disease and venous thromboembolism (blood clots in veins).

The same does not apply to other forms of estrogen. For instance, sublingual estrogen tablets dissolved under the tongue can largely sidestep the first pass and go directly into the bloodstream. As a result, they are less likely to cause the same complications as oral estrogen.

Transdermal estrogen patches can also bypass the first pass.

Estrogen injections also go directly into circulation, resulting in greater bioavailability (more active drug entering circulation) at lower doses. Because of this, an estrogen injection may only require 1 to 20 milligrams (mg) per week compared to oral estrogen which may require 2 to 8 mg per day.

Types of Estrogens

In addition to the different routes of administration of estrogen treatment, there are also different types of estrogens used for treatment. These include:

• Oral 17B-estradiol
• Oral conjugated estrogens
• 17B-estradiol patch (usually replaced every three to five days)
• Estradiol valerate injection (typically every two weeks)
• Estradiol cypionate injection (every one to two weeks)

Endocrine Society guidelines specifically suggest that oral ethinyl estradiol should not be used in transfeminine people. This is because oral ethinyl estradiol is the treatment most associated with thromboembolic events such as deep vein thrombosis, heart attack, pulmonary embolism, and stroke.

The goal is to make certain you have similar levels of estrogen to premenopausal cisgender women, which is about 100 to 200 picograms/milliliter (pg/mL). A doctor will also need to monitor the effects of your anti-androgen by checking your testosterone levels.

The testosterone levels should also be the same as for premenopausal cisgender women (less than 50 nanograms per deciliter). However, androgen levels that are too low may lead to depression and generally feeling less well.

Risks and Benefits

By Route of Administration

In general, transdermal or injected estrogen treatment is thought to be safer than oral treatment. This is because there is no hepatic first pass effect. Topical and injectable estrogens also need to be taken less often, which may make dealing with them easier. However, there are downsides to these options as well.

It is easier for people to maintain steady levels of estrogen on pills than with other forms of estrogen. This can affect how some people feel when taking hormone treatment. Since levels of estrogen peak and then decline with injections and transdermal (patch/cream) formulations, it can also be harder for doctors to figure out the right level to prescribe.

In addition, some people experience skin rashes and irritation from estrogen patches. Injections may require visiting the doctor regularly for people who are not comfortable giving them to themselves.

By Type of Estrogen

Oral ethinyl estradiol is not recommended for use in transgender women because it is associated with an increased risk of blood clots. Conjugated estrogens are not used frequently, as they may put women at a higher risk of blood clots and heart attacks than 17B-estradiol, and they also cannot be accurately monitored with blood tests.

Risk of thrombosis (blood clots) is particularly high for those who smoke. Therefore, it is recommended that if smokers wish to be on estrogen therapy, they use transdermal 17B-estradiol (patch) if that is an option.

Treatment and Gender Surgery

Currently, many surgeons recommend that transgender women and transfeminine people stop taking estrogen before they undergo gender affirmation surgery. This is because of the potentially increased risk for blood clots that is caused both by estrogen and by being inactive after surgery. However, it is unclear whether this recommendation is necessary for everyone.

Transgender women and nonbinary feminine people who are considering surgery should discuss the risks and benefits of discontinuing their estrogen treatment with their surgeon. For some, discontinuing estrogen is no big deal. For others, it can be extremely stressful and cause an increase in dysphoria. For such people, surgical concerns about blood clotting may be manageable using postoperative thromboprophylaxis. (This is a type of medical treatment that reduces the risk of clot formation.)

However, individual risks depend on a number of factors including the type of estrogen, smoking status, type of surgery, and other health concerns. It is important that this be a collaborative conversation with a doctor. For some, discontinuing estrogen treatment may be unavoidable. For others, risks may be managed in other ways.

A Word From Verywell

Transgender women and nonbinary feminine people taking estrogen treatment should be aware that they will need many of the same screening tests as cisgender women. In particular, they should follow the same screening guidelines for mammograms. This is because their breast cancer risk is much more similar to cisgender women than it is to cisgender men.

Research shows that any person with a prostate, including trans women on estrogen, can still get prostate cancer. However, there is currently no consensus on guidelines for how to screen for prostate cancer in this population and more research is needed in this area.