Disclaimer: This information is for educational purposes only and is not medical advice. Any decisions about hormone therapy or other medical care should be made by you in consultation with your healthcare team.
As a gender-affirming care doctor, I prescribe estradiol almost every day. Estradiol is a hormone the body produces naturally, and it is also available as a medication. As a medication, it can come in the form of pills, gels, patches, or injections. It’s a key part of hormone therapy for transgender women, but it’s also used for other purposes, like managing menopausal symptoms.
In people with ovaries, most estradiol is naturally produced there. People assigned male at birth also naturally have estrogen in their bodies. The main types are estradiol (E2) and estrone (E1), with estradiol being the most active. Most of this estrogen comes from the conversion of testosterone into estrogen in tissues such as fat, muscle, bone, and the brain. The testes also produce small amounts directly.
There are four different types of estrogen in the body:
- Estrone (E1): A weaker form of estrogen that becomes more prominent after menopause and is present in people assigned male at birth.
- Estradiol (E2): The most potent estrogen, responsible for most feminizing effects, and the form used in gender-affirming hormone therapy.
- Estriol (E3): A weaker estrogen that is produced mainly during pregnancy.
- Estetrol (E4): Produced only by the fetal liver during pregnancy and not normally found outside of pregnancy.
In gender-affirming hormone therapy, estradiol helps the body develop more typically feminine features and reduce masculine traits. It supports breast growth, shifts body fat to areas like the hips, thighs, and buttocks, softens the skin, reduces muscle mass, and can change body odor. It also works to slow or stop features like facial hair growth and male-pattern baldness. In some cases, estradiol alone may be enough to reduce testosterone without the need for additional testosterone-blocking medications, though these are often used to achieve more consistent suppression.
Estradiol works through three main mechanisms:
- Binding to estrogen receptors: Estradiol attaches to receptors in cells throughout the body. This turns on specific genes that encourage feminine changes, like breast development, softer skin, and fat redistribution.
- Suppressing testosterone production: Estradiol signals the brain, particularly the pituitary gland, to decrease testosterone production in the testicles. Estradiol alone is not always enough for full suppression, which is why antiandrogen medications are often prescribed alongside it.
- Rapid, non-genomic effects: Estradiol can also act on receptors located on the cell surface, triggering fast responses that don’t require changes in gene activity. These effects include adjusting blood vessel function, influencing how cells use and store energy, and activating signaling pathways that affect cell repair and communication. These responses happen within minutes.
Potential Health Risks of Estradiol
Estradiol is generally safe when prescribed and monitored appropriately, but it does carry some risks. At higher doses, or in people who have other risk factors for blood clots (such as a history of clotting disorders, smoking, or certain medical conditions), the risk of blood clots can increase. However, the form of estradiol used in hormone therapy—especially patches, gels, or injections—is generally considered safer from a blood clot perspective than the estrogen found in many oral contraceptives (the pill). Other possible side effects include headaches, mood changes, breast tenderness, or changes in blood pressure. Regular check-ups and blood work with your healthcare team are important to keep these risks low and ensure treatment is safe.
Whether you are a cisgender woman experiencing menopausal symptoms or a transgender woman pursuing feminizing hormone therapy, estradiol plays an important role in supporting physical changes, overall health, and well-being. Understanding how it works in gender affirming care—from promoting breast growth and fat redistribution to modulating testosterone levels and triggering rapid cellular effects—can help you make informed decisions with your healthcare team. Every person’s needs, goals, and responses to estradiol are unique, which is why ongoing monitoring and individualized care are essential. By learning about estradiol, you can approach hormone therapy safely and effectively, with a clear sense of what to expect and why it matters.
