How Do Doctors, Patients Manage Side Effects of Gender-Affirming Care?

How Do Doctors, Patients Manage Side Effects of Gender-Affirming Care?
How Do Doctors, Patients Manage Side Effects of Gender-Affirming Care?
Emma Yasinski
Emma Yasinski Staff Writer
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When Mel was first prescribed hormones in 2009, he wasn’t sure he planned to complete the transition to becoming a trans man. “My goal was to explore the gender spectrum through hormones. I wasn’t yet totally clear that I wanted to transition and make a full gender transition, but I definitely felt the need to move away from my identity as a woman,” he says. Working with his physician, he started by taking medicines to end his menstrual cycle and then began with  very low doses of testosterone, gradually increasing them over time. “As I started taking testosterone in small doses, I felt more and more comfortable in my skin.”

Today’s news is filled with stories about anti-transgender legislation and actions, but what does transgender care really entail? Are there side effects to gender-affirming care? Only about a quarter of nonbinary people choose to have gender-affirming surgery. Because MedShadow’s mission is to raise awareness about side effects of medicines, this article won’t go into detail about surgery, but it will focus on the benefits and side effects of gender-affirming medications, such as puberty blockers and hormones.

What Is Gender Incongruence?

Gender incongruence is a mismatch between the gender a person was assigned at birth and what gender they feel the most comfortable being. Studies have pointed to a variety of causes for the discrepancies, both genetic and environmental. Gender dysphoria, on the other hand, is a condition in which a person with gender incongruence feels distressed by this mismatch. Not everyone with gender incongruence experiences gender dysphoria.

What Is Gender-Affirming Care?

Experts emphasize that prior to puberty, gender-affirming care is really allowing a child to express themselves how they see fit, for example, by cutting their hair or growing it long and maintaining open and supportive communication. “Medical interventions are really not indicated before puberty,” said Jason Rafferty, MD, a pediatrician and child psychiatrist who authored the American Academy of Pediatrics recommendations for gender-affirming care in children and adolescents in a webinar for the Association of Healthcare Journalists.

Once a child reaches puberty, their healthcare team may prescribe puberty blockers and eventually hormone therapies. However, Joshua Safer, MD, executive director of the Mount Sinai Center for Transgender Medicine and Surgery in New York, explained in the same webinar, that a common misconception is that care is “one size fits all,” when, in fact, it’s very customized. He said, “People who are thinking about some linear process, where somebody gets a mental health clearance before they take hormones before they have a surgery, [are] really not understanding the diversity of people. [They are] failing to recognize how much we customize care and how varied people are in terms of what’s going to work for them.”

Rafferty added that many people believe that “once you start gender-affirming care, the train has left the station; you can’t turn it around. In my own practice, I have many patients who present to me where they initially come in and talk about feeling uncomfortable in their body and their gender.” It’s okay, he said, if they “don’t ultimately get to a place where they’re looking at surgery or being on hormones. The ultimate goal is affirming that the patient feels more confident in who they are.”

Side Effects of Puberty Blockers

GnRH agonists (gonadotropin-releasing hormones), also known as puberty blockers, have been used for decades in patients experiencing precocious, or early, puberty, explains Tamar Reisman, MD, an endocrinologist at the Mount Sinai Center for Transgender Medicine. “Basically, it reversibly shuts off the hormone access. It prevents puberty from happening while you’re on it, and that buys you a little bit of time to just figure things out.”

For adults who are prescribed a GnRH agonist such as Lupron, you may experience menopauselike symptoms, such as hot flashes and migraines. Mel says, “Even though I expected it, I was relatively young to [be going through menopause]. And you know, there are physical effects. Having a hot flash in the middle of a meeting, as most women will tell you, is not the easiest thing to do. But you do figure it out over time. And then once I started with testosterone, it was such a relief.”

For adolescents, however, menopauselike symptoms are less common. The drugs can be administered a variety of ways, but one of the common strategies is through an injection. Any time you receive an injection, you could experience injection-site reactions, such as redness, swelling and pain.

Reisman says the main concern with puberty blocking in adolescents is limited data on the long-term effects of delaying puberty. For example, sex hormones help with building bone and most people build up the majority of their bone mass before age 25. “If you’re missing out on a few years of bone-mass accumulation, what does that mean for these patients when they’re 60, when they’re 70?” asks Reisman. She’s seen evidence that bone accumulation begins to “catch up” when you stop GnRH agonists or start taking hormones, but “the question is when you’re 65, do you get a hip fracture? That’s the kind of data we really need.”

Scientists are getting closer to collecting that data. Individuals assigned female at birth who used puberty blockers and then received testosterone therapy had normal bone density years later (the average age at follow up was 28 years old), according to a 2023 study of 75 people with gender dysphoria. However, people assigned male at birth who used puberty blockers and then received estrogen therapy had lower bone density scores specifically in the lumbar spine or lower back (bone density of two other regions—the hip and the part of your upper thigh bone that connects with your hip—were healthy.) “These findings suggest that treatment with GnRH agonists followed by long-term GAH is safe with regard to bone health in transgender persons receiving testosterone, but bone health in transgender persons receiving estrogen requires extra attention and further study,” the study authors wrote. They also suggested that certain lifestyle adjustments, such as lifting weights, avoiding smoking and supplementing with vitamin D could help strengthen bones.

Gender-Affirming Hormone Therapy

After puberty blockers, you and your physician may discuss gender-affirming hormone therapy. There are different regimens for masculinizing and feminizing hormones.

Masculinizing Therapy

Those who start masculinizing therapy are given testosterone. Everyone is different, and it may take some time to get your testosterone levels up to the range that’s right for you. An average man can have a wide range of natural testosterone levels, from about 300 to 1000 nanograms per deciliter (ng/dL).

The hormone can be administered via injection, a topical gel, a patch or a pill. “Injections are probably the most common, but there’s no real reason you can’t receive it another way,” says Reisman.

Your healthcare team will take regular lab tests to measure your testosterone level and determine when you start to reach the middle of that range. Reisman says that once you’ve reached the desired level, you’ve found your dose. You are unlikely to require a change of dose unless you have a dramatic weight change or are prescribed other medicines that interfere with metabolism.

You and your healthcare team can work together to decide how quickly to raise your dose. Mel, for example, took the transition slowly, starting with very low doses of testosterone, increasing them very gradually.

You usually start noticing physical changes, such as beard and body hair growth, fat redistribution, voice dropping to a lower register and clitoral growth within three months to three years of taking testosterone.

“For those early months of treatment, I definitely experienced a different way of seeing things. It was surprising how much things changed,” says Mel, explaining that the most surprising part was the number of things he saw in a more sexual context. “But then I acclimated, and not just in terms of sexuality, [but also] physicality, [I was] feeling stronger, feeling more able, more capable, more willing to move things around or take on physical challenges that I might not have taken before.”

Side Effects of Masculinizing Hormones

In addition to desired physical changes, the treatments can cause acne and male pattern hair loss. You may also experience an increase in urinary tract infections, vaginal atrophy or dryness. If these symptoms become problematic, Reisman says, you may be prescribed a low dose of intravaginal estrogen.

While your team is still working to find your ideal testosterone dose, one of the more common side effects is an increase in red blood cells called erythrocytosis. This condition can cause headaches, shortness of breath and nosebleeds. They can also raise your risk of blood clots. “This is very much dose dependent,” says Reisman. “That’s precisely why we monitor patients. It’s exactly why you go to the doctor to get hormones and don’t just order stuff online. If we monitor for it and find it, we can adjust your dose.”

Does Taking Testosterone Inhibit Fertility?

There isn’t much data available about long-term fertility for patients who take testosterone. Still, some trans men successfully get pregnant after they pause hormone treatment for a few months. “In my own experience, I’ve had several patients who take testosterone stop hormones for a couple of months, have a kid and go back on hormones,” Reisman says. She adds that there are about 55 cases in the medical literature of transmasculine patients who have become pregnant. The cases are reassuring, however, Reisman says, “We counsel all our patients to think about doing fertility preservation and egg freezing before starting hormone therapy.”

Feminizing Therapy

There are two aspects of feminizing therapy. First, you have to suppress testosterone; then you have to increase estrogen.

Side Effects of Testosterone Blockers

To suppress testosterone, doctors will often prescribe the diuretic spironolactone. The drug is also used to treat high blood pressure, heart failure and hirsutism that accompanies polycystic ovarian syndrome (PCOS). Reisman says, “It’s a blood pressure medication and diuretic that we use as a testosterone blocker, so a lot of patients have side effects related to that aspect of it. Peeing a lot, electrolyte abnormalities, high potassium levels (which can cause weakness, fatigue and, in very extreme cases, heart attacks), dizziness, lightheadedness, muscle cramps.” She adds that these side effects are rarely problematic when patients are young and have healthy kidneys; the best thing patients can do while using the drug is to stay hydrated.  However, Reisman recommends, to switch to another medication, if a patient is having lots of problems with it.

One common side effect of suppressing testosterone is sexual dysfunction. This can include low libido, erectile dysfunction and difficulty climaxing. A 50-something trans woman who had surgery about 30 years ago, wrote in the Washington Post, “The surgeon deemed my operation a good outcome, but intercourse never became pleasurable.”

Side Effects of Estrogen

To raise estrogen levels, doctors usually prescribe the hormone 17 beta-estradiol. “Like the masculinizing hormone regimens, we’re looking for certain numbers as our target,” says Reisman. She says she aims for her patients to have testosterone levels under 50 ng/dL and estradiol levels around 100 or 200 picograms per milliliter (pg/mL). Like testosterone, the hormones can be administered via patch, pill or injection.

“Probably the most feared side effect with estrogen is blood clots,” she says. This is also a known possible side effect of taking birth control pills. The patch offers a lower risk of blood clots than the pill, she explains, so if you’re at risk, this may be a better choice for you. Additionally, it’s important not to smoke, as that can raise your risk for blood clots even higher. Some other side effects of estradiol include: increased hunger, headaches or migraines, and more cheerfulness or crying. “The way it’s been described to me is not so much depression or sadness, just that emotions are closer to the surface. And crying becomes easier,” says Reisman.


Some trans women are prescribed progesterone to supplement their estradiol and increase feminization. While it seems to be getting more popular, says Reisman, doctors at Mount Sinai don’t prescribe it, because there isn’t enough evidence of its efficacy. She adds that they don’t want to risk that the treatment could raise the chances of patients developing cardiac events or breast cancers as they age. A study of hormone replacement therapies on post-menopausal cis women has suggested it might. 


Some studies have analyzed the semen of transgender women while they’re taking hormones. It’s known that hormones reduce sperm quality. “You need testosterone to be fertile and it needs to be your own,” says Reisman. She always counsels patients about fertility and the option of freezing sperm. “I would never ever want to deny somebody the opportunity to have biological kids if that’s their goal.”

Transgender Care in the Long Run

Reisman says it’s crucial for transgender patients to get regular cancer and health screenings. If you have breasts, you need age-appropriate breast cancer screenings. “If you have a body part, regardless of your gender identity, you need age-appropriate cancer screening. So regardless of your gender identity, if you have a cervix, you need [regular] Pap smears,” says Reisman.

Are Hormone Therapies Reversible?

The effects of puberty blockers are reversible. As for hormone therapy, it often depends on how long you’ve been on the treatments. For example, if you start growing facial hair and developing a deeper voice while taking testosterone, that may not go away. “But most of the rest of the impact of testosterone is reversible, especially at those younger ages, including male pattern baldness and shifts to fertility,” says Safer.

Often, says Rafferty, when a patient decides to stop taking hormones, it’s not because they hope to revert to the gender they were assigned at birth, but because they identify as nonbinary. “Some of those more permanent effects of testosterone are not something that necessarily they see as sort of detrimental or negative. 

He adds, “I always tell my patients it’s not like one day you make a decision, [and] you have to live with it. You make this decision every time you come to the clinic. We want to know if something doesn’t feel right, and we will work with you to correct that whether it’s your first day in clinic, or whether that’s 10 years in clinic.” 

Mel says, “If it’s right for you to transition, it feels right.”

For more information about transgender care, check out guidelines from the University of California San Francisco and the Endocrine Society. For a more in-depth discussion of mental health in regards to transgender identity and transition, check out reporting from undark.org.



Cis, or cisgender: a person whose gender identity aligns with the gender they were assigned at birth. A person who was assigned male at birth and still identifies as male, or someone who was assigned female at birth and still identifies as female.

Gender-affirming care: treatments ranging from therapy to hormones and surgery, that support a person’s gender transition.

Gender dysphoria: a condition in which a person with gender incongruence feels distressed by this mismatch.

Gender identity: an individual’s sense of their own gender.

Gender incongruence: a mismatch between the gender someone was assigned at birth and how they feel.

Nonbinary: a person who does not feel completely aligned with either the male or female gender.

Trans man: a person who was assigned female at birth, but identifies as male.

Trans woman: a person who was assigned male at birth, but identifies as female.

Transfeminine: a person who was assigned male at birth but identifies more with a feminine identity.

Transgender: a person who identifies as having a gender different from the one assigned to them at birth.

Transition: the process in which a person shifts to living as a different gender than the one assigned at birth. This can include social changes and medical interventions.

Transmasculine: a person who was assigned female at birth, but identifies more with a masculine identity.


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