The hormone replacement therapy, or HRT, that Army Pfc. Bradley Manning has requested alters the body’s balance of sex hormones — estrogen for male-to-female and testosterone for female-to-male transitions. Sometimes, male-to-female patients will also be given progesterone, another steroid typically produced by the ovaries, as well as a testosterone blocker such as spironolactone.

“It basically initiates a second puberty. The full effects of that will typically take two to three years,” said Marci L. Bowers, a California-based gynecologist and surgeon who has performed hundreds of gender-change operations over the past decade.

Not all patients getting hormone replacement therapy have surgery, either because of cost or personal preference.

Hormones are the chemical messengers of the body that travel through the bloodstream and send signals to various organs, affecting growth, metabolism, reproduction and mood. Even small changes can have big effects; for instance, during menopause, a woman’s body slowly produces less estrogen and progesterone, leading to hot flashes and thin bones.

Continuous doses of female hormones will cause a male to see changes within the first few months of therapy such as softer skin, fat and muscle rebalancing, and breast development. Those changes start to become irreversible within six to nine months.

The degree of effects of hormone therapy varies considerably among individuals. For example, the younger a patient starts hormones, typically the better they work, said Grace Kim, a District-based psychologist who has a number of transgender patients. Bowers added that many patients continue some form of hormone therapy after surgery.

It is not known whether Manning, who has not started hormone therapy, will be allowed the medication while incarcerated. Manning was sentenced this week to 35 years in military prison for giving classified documents to the anti-secrecy group WikiLeaks.

JoAnne Keatley, the director of the Center of Excellence for Transgendered Health at the University of California at San Francisco, calls the medication “very expensive.” It can run about $400 a month for those without coverage or whose insurance won’t cover it. The hormones may come in pill or injectable form.

“It’s a legitimate medical treatment that [patients] need access to, and being without it can lead to negative health outcomes including suicide,” Keatley said.

However, HRT has its limits — which is where reconstructive surgery can come into play. Masculine characteristics such as height, facial features and voice are not affected by changes in sex hormones. The Philadelphia Center for Transgender Surgery, one of only a handful of such clinics in the nation, performs breast augmentations and genital surgeries, as well as facial feminization procedures tailored to patients’ needs.

At the Philadelphia site, the total cost for male-to-female surgery is $19,150, which covers the surgery, operating room and anesthesia fees, and three days in the hospital, according to the clinic’s Web site.

But before surgery, patients must live in their preferred gender role for at least a year and typically undergo hormone therapy during that time, Bowers said. A psychological evaluator will typically recommend the hormones, which are prescribed by a doctor.

Before allowing a patient to go through genital surgery, the Philadelphia Center for Transgender Surgery generally requires hormones for a year, presenting full time as the other gender for a year, and letters from two mental health specialists.

One of the center’s most notable patients is Renee Ramsey, an ex-GI and Green Beret who wanted to transition to a female her entire life. In 2007, the then-76-year-old had her first operation performed by surgeon Sherman N. Leis. At the age of 80, she completed all her surgical procedures.

The American Psychiatric Association — in its most recent edition of the guidebook the
Diagnostic and Statistical Manual of Mental Disorders, used by psychiatrists and other mental health clinicians — revised “gender identity disorder” to “gender dysphoria.” The term is used to diagnose people whose gender at birth is contrary to the one they identify with. A psychologist who evaluated Manning in Iraq diagnosed him with a gender identity disorder in 2010.

Kim, who has a number of transgender patients, said the change in terminology represents a shift away from gender issues being pathological and removed the connotation that the patient is “disordered.”

“Questioning your gender identity isn’t of itself a problem,” she said.

D.C.-based psychotherapist Mike Giordano agreed: “People need to understand that someone else’s gender identity and their expression is actually not up for debate, and people are who they are.”

Lenny Bernstein and Brady Dennis contributed to this report.