For many transgender men and women, hormone replacement therapy is an important component of their transitioning process, allowing them to develop physical traits aligned with their gender identity. Taking this step to feel more comfortable in your body is a big decision, and there are many factors to consider as you determine if gender-affirming hormone replacement therapy is right for you. 

Below is an overview of hormone replacement therapy medications and side effects to help you learn more about the process.

Hormone replacement therapy for transgender women

Estrogen and testosterone-blocking medications help transgender women develop a more feminized appearance in line with their gender identity while transitioning. It reduces the discomfort of gender dysphoria, the distress caused by having a gender identity that differs from the sex you were assigned at birth. Many transgender women experience less emotional distress, improved personal relationships, and a better overall quality of life as a result of hormone replacement therapy.

Feminizing hormone replacement therapy causes a variety of physical changes like breast development and facial and body hair reduction. You may also experience a loss of muscle tone and changes in your body shape as the body redistributes fat cells.

Feminizing hormone replacement therapy medication and timing

While your healthcare provider will help you develop an individualized treatment plan, feminizing hormone therapy often begins by taking 100 to 200 milligrams daily of a diuretic called spironolactone to begin blocking male hormone receptors and suppress testosterone production. Some individuals begin taking estrogen immediately, in tandem with spironolactone, to further reduce testosterone production and develop more feminine characteristics. In other cases, estrogen is introduced after several weeks of spironolactone use. Your doctor will recommend the best plan for your needs.

There are various methods for administering estrogen, including orally, by injection, or as a cream, gel, spray, or patch. Commonly used forms of estrogen during a male-to-female transition include:

• Oral: Estradiol tablets.
  Note that your doctor may advise you to let the tablets dissolve under your tongue rather than swallowing them. This is called sublingual administration, which may lower your risk for blood clots since it bypasses the liver.

• Injections: Estradiol valerate (branded options include Delestrogen®) and estradiol cypionate (branded options include DEPO®-Estradiol)

• Patches: 17B-Estradiol patch

Feminizing hormone replacement therapy side effects

You may experience one or more of the following hormone replacement therapy side effects. Your doctor can advise you about the potential risks and benefits prior to starting hormones.

• A blood clot in a deep vein (also known as deep vein thrombosis) or in your lungs

• High levels of triglycerides, a type of fat found in the blood

• Weight gain

• High potassium levels

• High blood pressure

• Reduced libido

Feminizing hormone replacement therapy may also increase your risk for some chronic health conditions. Since estrogen affects how your body responds to insulin, it can lead to changes in your blood sugar levels and a greater risk for type 2 diabetes. Research into the impact of estrogen on your cardiovascular system is ongoing, and some studies have found a connection between estrogen therapy and a greater risk for heart disease and stroke. You may also face a greater risk of breast cancer after starting hormone replacement therapy.

Certain underlying health conditions may increase your risk of health complications related to the use of estrogen and testosterone-blocking hormones. It’s important to share your full medical history with your doctor, especially if you’ve had a hormone-related cancer, like prostate cancer, or a history of blood clots.

Feminizing hormone therapy and fertility

Gender-affirming hormone replacement therapy may affect your fertility, as it impacts sperm production. While some transgender women can produce sperm again after stopping hormone treatment, research indicates that this may not be the case universally, and there is a risk of permanent infertility with long-term use of hormones. If you would like to have biological children, ask your doctor about your options with freezing your sperm before starting hormones.

Hormone replacement therapy for transgender men

Hormone replacement therapy for transgender men during a female-to-male transition also combats gender dysphoria, leading to reduced emotional discomfort and better overall mental health.

During the process, you will take testosterone, which decreases estrogen production and suppresses menstruation. Testosterone is typically administered by injection (branded options include Delatestryl® and Tesamone®) or as a gel applied to the skin (branded options include AndroGel®, Testim®, Fortesta®, and Axiron®). In some cases, it may be applied as a patch or pellets positioned under the skin. If you have a persistent menstrual flow, your doctor might recommend taking progesterone to control it.

You may observe some of the following physical changes within several months of starting hormones, though individual responses to treatment varies:

• Deepening of the voice

• Facial and body hair growth

• Body fat redistribution

• Increased muscle mass and strength

Masculinizing hormone replacement therapy side effects

There are several potential side effects that transgender men may experience as a result of hormone replacement therapy, including the following:

• Overproduction of red blood cells

• Blood clot in a deep vein or lung

• Weight gain

• Pelvic pain

• Sleep apnea

• Abnormal cholesterol levels

• High blood pressure

Masculinizing hormone replacement therapy may also increase your risk for type 2 diabetes and cardiovascular disease.

You are more likely to experience one or more of these health complications if you have had breast cancer or have a history of blood clots. It may be unsafe to continue with hormone treatment if you are pregnant or breastfeeding. Be sure to discuss the potential risks and benefits of hormone replacement therapy with your doctor, and make sure they are aware of your full medical history.

Masculinizing hormone therapy and fertility

While some transgender men have sucessfully undergone egg freezing or IVF after starting hormone therapy, long-term use of hormones may lead to permanent infertility. If you want to leave open the possibility of starting a family by having children biologically, consult your doctor about your options for egg freezing before starting treatment.

Given that individual responses to testosterone treatment vary, you have a chance of becoming pregnant even while taking hormones. Your doctor can advise you about your options for birth control.

Baseline and follow-up testing for hormone replacement therapy

Before you begin hormone replacement therapy, your doctor will order tests to measure your baseline lipid, blood sugar, liver enzyme, and electrolyte levels, which may change throughout the course of your treatment. Your doctor will also evaluate your medical history to identify any health conditions that may affect treatment. This is also a good opportunity to discuss reproductive health and fertility considerations, including potential contraception options if you are a transgender man.

Throughout hormone therapy, you will have regular follow-up appointments with your healthcare provider to document physical changes in your appearance and monitor the impact of hormones on your lipids, blood sugar, and liver enzymes.

Hormone replacement therapy affects you emotionally as well as physically. In the long term, gender-affirming treatment, including both hormone therapy and surgery, can lead to better mental health, reducing the need for depression and anxiety-related treatment.

Your doctor will likely ask questions related to your mental health during your initial consultation — including any symptoms of gender dysphoria that you have experienced and how they impact you at work, school, or home — and continue the conversation throughout your treatment.

It’s important to be honest with your doctor about how you are feeling — your mental health matters as much as your physical health. Don’t be afraid to ask for mental health-related resources if you need extra support, and remember that your doctor is here to help you without judgment.

View the National Institute of Mental Health’s suggestions for finding mental health treatment, and the Human Rights Campaign’s list of LGBTQ mental health resources.

A pharmacy partner you can rely on

Alto is here to support your journey with hormone replacement therapy. Our team of patient care pharmacists has experience working with the LGBTQ+ community and is available to answer any questions you have about the process.

We also make it as simple as possible to stay on top of your medications, with same-day delivery and mediation management tools like reminders and auto refills in our app. Reach out any time to get started by phone at 1-800-874-5881 or download the app for secure messaging with our care team.

This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition.