Last of a three-part series.

BOSTON — Jackie cocks her head to one side, trying to recall the first clue that her daughter Natalie wanted to try life as a boy.

"I found something on my Amazon account," Jackie says. "She had used my Amazon account to buy a binder, so I thought it was a binder for school.”

Jackie giggles as she remembers mentioning the bill to Nate.

Nate at his home in Boston. (Jesse Costa/WBUR)

"'Oh, you should tell me,' " Jackie says she told Nate. "'I go to Staples all the time. I’ll get you some binders.' "

Nate muttered something about it being a different kind of binder.

Then Jackie noticed the charge: $39.95. The product link opened to a picture of a female wearing a thick elastic band that made her chest nearly flat. Breast binders are a common early step for females transitioning to male, but they come with health risks.

Dr. Ralph Vetters, who treats transgender teens at the Sidney Borum Jr. Health Center in Boston, says binders make breathing more difficult, increase the risk for lung infections and, "by compressing the breasts, they can cause a sort of fibrosis. Scars may be a word for it. It hurts."

The alternative for transgender men — females transitioning to male — is surgery that pulls tissue out of the breast. The procedure costs $5,000 to $10,000 and is only covered by a handful of employers in Massachusetts. (Harvard University, where both of Nate's parents work, covers transgender medical procedures.)

Teenagers need a parent’s permission for surgery and any other transgender medical treatment before the age of 18. Some doctors refuse to help patients of any age make such a fundamental change. Leonard Glantz, who teaches bioethics at the Boston University School of Public Health, says the main concern is surgery that removes a healthy penis, ovaries or breasts.

"Is it surgery to fix a medical condition?" Glantz says, explaining the dilemma for many physicians. "Is it some form of cosmetic surgery, or is it mutilation?"

The Catholic Church comes down on the side of mutilation. John Haas, president of the National Catholic Bioethics Center, says the church hopes that all children will flourish in the image of God as created at birth.

"If they are surgically mutilated," Haas says, "that clearly would violate their best interests and it probably would not be in the best emotional health to be dressing up as the opposite gender and acting out in that way."

Not all objections are based on religion. Physicians are trained, Glantz says, to remove diseased tissue such as lesions and tumors. "That's the moral question," he says. "Does one remove normal tissue in order to change the body that someone was born with and create a new body that is supposed to be more in line with their actual sex?"

For parents, these questions have additional complications. Some procedures — such as top surgery to remove or build out the breasts — are reversible, so parents may feel more comfortable beginning the medical journey there. But many of the effects of hormone therapy can't be reversed. Nate, who began his transition two years ago, has not had any surgery but he has asked to begin taking testosterone. So far, his parents have said no.

"So much has changed in my life since I was a teenager," says Nate's dad, Tom. "I never wanted to have kids. I didn’t even think I wanted to get married."

So how, Tom wonders, can Nate be sure he won’t regret beginning testosterone as a teenager? Within months of starting weekly shots or a daily cream, Nate’s vocal cords would get longer and thicker, giving him a deeper voice. He would see new facial and body hair, all permanent changes. And the increased testosterone in Nate’s body might make him infertile.

"Even if you stop taking it, there are things that don’t change," Tom says, throwing up his hands. "I also don’t think they know everything they think they know about hormones and how they affect bodies — and will these kids all develop cancer?"

The short answer is no. There is no indication that long-term hormone use increases the risk of cancer for transgender men or women, but there’s very little rigorous research. However, transgender men and women do face an increased risk of heart disease, Vetters says.

Nate’s parents have a lot of worries. What if they let Nate make permanent physical changes and then he changes his mind? In thinking about this, Jackie slips back to referring to Nate as a girl.

"I said to Natalie yesterday," Jackie says, "'I need to look you in the eye when you’re 30 and say I thought this through really hard and I got all the information I could get and I made the best decision I could make for you as your mother.' There’s no way she’s going to look at me at 30 and say, 'At 16, Mom, I was old enough.’ There’s no way. But she might say, 'Why the hell did you let me do that?' "

How do parents know if their children are ready to make a permanent gender change?

"Almost everybody who’s looked at this has said that the defining time is puberty," says Dr. Norman Spack, who began treating transgender youth at Boston Children's Hospital in 1998.

"The difference between a tomboy and a trans-male who starts puberty is that the tomboy accepts having breasts, accepts having periods," and the trans-guy does not, Spack says.

"If your body’s already somewhat alien because it has or hasn’t got certain body parts and then those things grow or other things grow, that’s when patients really decompensate psychologically," Spack adds.

Spack sees young girls who cut themselves monthly, with every period. Children and teenagers who seek help from Spack’s clinic are generally referred to a counselor outside the hospital for six months to a year. If the counselor decides the patient is ready for treatment, Spack’s team begins a series of tests and their own counseling evaluation. If Spack is persuaded that a teenager is ready to change genders, he prescribes hormones that launch the transition.

How often is he wrong?

"Those who are sent to us, with parental support, who have had the counseling and go through the psychological testing, are virtually always the real deal," Spack says. "Out of like 170 kids, we’ve only had one who changed her mind while on the pubertal blockade," or drugs that adolescents take to put off the definition of male and female characteristics — but more on that in a moment.

On the question of whether transgender men and women ever change their mind, yes, you may have heard some of the stories. But doctors say that these patients did not go through rigorous tests and counseling. Very limited research, from Sweden and the Netherlands, has found that most patients who had sex reassignment surgery did not regret the change. But a United Kingdom survey that included residents in early stages of the transition, such as changing their name, did find significant instances of regret. There are no long-term studies of transgender men and women who've had sex reassignment surgery or hormone therapy in the U.S.

Disputes In Transgender Medicine

In the second floor apartment of a triple decker in Revere, 22-year-old Logan Ferraro rips open the package of a syringe, attaches a needle and pokes it into a vial. He draws a dose of thick, clear liquid. Ferraro dreads giving himself these weekly shots of testosterone.

"The hardest part is to get it to break through the skin," he says, pinching a roll of flesh near his belly button and pushing the needle in at an angle.

Logan Ferraro, 22, prepares a hormone injection. He started testosterone fives years ago while still in high school and says the transition has been tough. (Martha Bebinger/WBUR)

Ferraro started testosterone five years ago, while still in high school. He says making the transition from female to male has been hard.

"Had I not truly believed that this was right, it would have been hell," Ferraro says. "I never would have wanted to do it. All I think about is sex, I have hair growing in weird parts of my body, your beard comes in all patchy and you get acne, like really bad acne."

Ferraro was never on the puberty blockers. These powerful drugs postpone puberty, giving parents and their children more time to make a decision about the child's adult gender. Today, use of these drugs in younger and younger children is one of the main controversies in transgender medicine.

"How low do you go?" asks Dr. Ken Zucker, who runs a gender identity clinic in Toronto. He worries about blocking puberty for 8-, 9- and 10-year-olds. He encourages parents to raise their children by their sex at birth until they reach puberty. That is, Zucker says, unless the child has "crossed the line" and is firmly established in the opposite gender.

But other doctors argue that earlier treatment is important to give girls becoming boys more height, and to help boys becoming girls pass later in life as a woman.

"Someone who’s gone through puberty as a male," Dr. Vetters explains, "[with] the larger forehead, the Adam’s apple, the wider shoulders — those create barriers to the ability of the individual to be perceived easily as female."

Vetters says transgender women have higher rates of smoking, substance abuse and suicide than do transgender men because it’s harder for a man to pass as woman. But treatment of children under the age of 12 varies from clinic to clinic. Some discourage transgender behavior in children while others support it or even, according to some critics, promote it.

Psychiatrist Jack Drescher says the wide variation is a problem "because really what’s happening is that all the centers have their own point of view and there tends, in my opinion, to be a lot of ideological thinking about how to proceed."

Drescher, who’s become a sort-of spokesman for the American Psychiatric Association on transgender issues, is trying to launch more ethical debates about what’s best for transgender children.

These issues are playing out as the number of clinics opening to treat transgender children and teenagers grows and demand for appointments explodes. Dr. Zucker, whose Toronto clinic is the largest in North America, has a waiting list of 75 to 100 patients.

"We are now in an era where the number of adolescents being referred for gender dysphoria is going through the roof," Zucker says.

Gender dysphoria is the formal diagnosis for people whose gender at birth doesn’t match the one they are living with now. There is no definitive research about what causes someone to want to change their gender and no research that proves more people are identifying as transgender. Zucker says he sees more children because the media and pop culture are bringing the topic to the forefront, and because they have easy access to information on the Internet.

Zucker says there is a noticeable increase in teenage girls who say they want to become boys. He isn't sure why, but says there is some indication that these girls "develop the perception that being a lesbian is heavily stigmatized. They realize that if they present in the male gender role and have a girlfriend they are left alone more and it's safer." This is just a theory. But it's one I heard several times while reporting this story.

'Looking For Certainty Where It Doesn’t Exist'

What feels like a sudden burst of interest in transgender medical treatment leaves many parents dazed and confused. Jackie, Nate's mom, is struggling to find the best way to support him, while still being a responsible parent in making decisions about hormones.

"I don’t know if I’m just being the ignorant mother who’s saying, ‘Dammit, not my kid,’ " Jackie says, slapping her leg. "I’m delighted for Nate to be a boy if we’re sure. But I’m totally torn about it."

Jackie wants evidence, some research that will tell her what Nate’s life and health might look like in 20 years.

“You’re looking for certainty where it doesn’t exist,” Dr. Drescher says when I keep asking if he knew of any such research. Dozens of transgender teenagers I spoke to about this story don’t seem bothered by uncertainty. But for their parents and other adults in their lives, this uncertainty is very difficult.

WBUR reporter Martha Bebinger will moderate a live chat at noon on Friday, Jan. 24 to answer any questions you might have about transgender or genderqueer issues. Ask your questions in advance here.