Laird Harrison

October 03, 2013

Jennifer Burnett, MD, knows firsthand the agony of being a woman trapped in the body of a man.

"It tears you apart," she told Medscape Medical News. "It makes your life hell."

Having made the transition from one sex to the other, the associate professor at the University of California, San Francisco, has dedicated much of her practice in Fresno, California, to helping others in similar circumstances.

Dr. Burnett described her success in treating male-to-female transsexuals at the American Academy of Family Physicians 2013 Scientific Assembly.

She combines an estradiol valerate 40 mg intramuscular injection self-administered every 2 weeks with a medroxyprogesterone acetate 150 mg intramuscular injection administered every 3 months during an office visit.

Patients continue on estradiol valerate indefinitely, but usually discontinue the progesterone after 2 years.

Dr. Burnett has been using this protocol for about 8 years.

However, it poses some risks, according to Neil Goodman, MD, a reproductive endocrinologist from Miami, and spokesperson for the American Association of Clinical Endocrinologists. "I have great concerns about this," he told Medscape Medical News.

Medroxyprogesterone can reverse the cardiovascular protection afforded by estrogen and can cause fluid retention and mood swings, he explained. It has been linked to breast cancer in women; "I have no idea what the long-term adverse effects will be on men," he said.

Controversial Approach

Dr. Burnett acknowledged that the use of medroxyprogesterone is controversial. "When I pioneered this, many people didn't think progesterone was a good idea," she noted. "I was able to show that using not only estrogen but also medroxyprogesterone produced much better changes in the breast."

The progesterone produces substantial changes in the nipple and areola not possible with estrogen alone, she explained. Estrogen and progesterone both suppress testosterone, but the suppression is better with the 2 hormones than with estrogen alone, she said.

Dr. Burnett prefers administering the estrogen by injection because oral estrogen has to pass through the liver. About half of it disappears there, so patients must take twice as much to achieve the same serum level, she explained. In addition, oral estrogen can cause the liver to produce multiple proteins, including coagulation factors that can cause thrombosis.

Because oral estrogen is associated with first-pass liver abnormalities and a higher dose is needed to achieve benefits in transsexuals, Dr. Goodman said he prefers a transdermal administration using a gel, cream, patch, or spray, over an injection. "The problem with injections of estradiol is that you don't have a steady state," he said. "The estradiol goes up and down following each injection."

Some transsexuals use spironolactone to suppress testosterone, but this is expensive and can cause changes in electrolytes, such as potassium, which sometimes lead to arrhythmias, said Dr. Burnett.

She presented data from 35 patients treated with estradiol and medroxyprogesterone at the scientific assembly here in San Francisco. Participants ranged in age from 17 to 56 years; 16 were Hispanic and 19 were non-Hispanic.

After an average follow-up of 23.7 months, 94% reported increased satisfaction with their breasts, compared with their satisfaction before beginning the protocol.

Table. Breast Satisfaction After Estradiol and Medroxyprogesterone

Breast Satisfaction Percent
Not as good, worse 0
Same 6
Better 28
Much better 66


None of the patients experienced significant complications, although 1 discontinued the protocol because of telogen effluvium.

About two thirds of the patients had previously used hormones, often obtained on the black market, Dr. Burnett reported.

"If they can't find a doctor to help them, they will seek out information on the Web," she said. "There is good information on the Internet, but there is also bad information. A lot of people end up doing a lot of harm to themselves."

Not only is self-treatment more dangerous, it is also more expensive, she noted. The total cost for a year of her protocol is about $230, which includes quarterly office visits. Estradiol valerate costs $39 for a 10 cm³ vial, she said.

When I pioneered this, many people didn't think progesterone was a good idea.

In contrast, the typical cost of self-treatment with Perlutal — a combination of hormones sold in some Latin American countries that is available on the black market — ranges from $360 to $720 a year.

Another advantage of her protocol is that it allows patient education to be incorporated into the office visits and affords access to HIV tests and other screening programs, Dr. Burnett noted.

However, 2 years of follow-up data is not enough to establish safety, especially in a relatively small population, said Dr. Goodman.

He said he prefers to use leuprolide acetate to suppress testosterone, in combination with transdermal estrogen.

He acknowledged that leuprolide is expensive — more than $800 a month — but argued that its safety profile is better understood because it has been used over the long term to suppress testosterone production in patients with prostate cancer. That hormone suppression is an important treatment benefit for male-to-female transsexuals.

For those who can't afford leuprolide, he suggested an oral estradiol and a different daily oral progestin, such as norethindrone or drospirenone, which have long-term safety data because they are used to treat menopausal symptoms.

Dr. Goodman emphasized that family physicians should not prescribe hormones for transsexuals until the patient has been seen by an endocrinologist.

Dr. Burnett and Dr. Goodman have disclosed no relevant financial relationships.

American Academy of Family Physicians (AAFP) 2013 Scientific Assembly: Abstract 114. Presented September 25 - 28, 2013.


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