This article is a collaboration between MedPage Today and:

CHICAGO -- Simply giving estrogen to male-to-female transgender patients won't completely suppress testosterone levels, researchers reported here.

In a study from a single-center experience, patients achieved good estrogen levels but only about half reached sufficient testosterone suppression with estradiol with or without a progestin, Matthew Leinung, MD, of Albany Medical College in New York state, reported at the joint meeting of the Endocrine Society and the International Congress on Endocrinology here.

Adding the anti-androgens spironolactone or finasteride didn't help, and actually appeared to slightly raise testosterone levels, Leinung reported.

"I don't know why I found what I found," he said during an oral presentation. "I don't have a good explanation because that's not what the conventional wisdom is."

There are many treatments for male-to-female transgender patients, but the optimal regimen isn't established because of a lack of evidence. Transgender medicine guidelines agree that, in general, patients should be brought into normal hormone levels for their desired gender, and that suppressing endogenous gonadal function is essential.

To get a better understanding of the hormonal response to oral estradiol in male-to-female transgender patients, Leinung assessed all patients seen at his transgender clinic from 2008 through 2013 (He picked 2008 as baseline because a major switch from ethyl-estradiol to oral estradiol occurred at that time).

His therapeutic strategy was to titrate all patients to 4 or 6 mg of oral estradiol, adding 2.5 to 10 mg of medroxyprogesterone if testosterone levels weren't sufficiently suppressed.

He said he would also add spironolactone or finasteride to lessen body hair, without regard to testosterone levels.

During that time, Leinung saw 162 male-to-female transgender patients, but ultimately used data from 82 of them. He excluded those who hadn't been on estradiol therapy long enough, who weren't on full doses, who had gender reassignment surgery, or who had been on Premarin.

He found that 46% of patients started on the 4-mg dose (6/13) had their testosterone levels sufficiently suppressed, below 100 ng/dL.

Six of those patients not suppressed on 4 mg went up to 6 mg, but only three of these patients subsequently achieved testosterone suppression.

For those started on 6 mg of estradiol, 52% had sufficient testosterone suppression. Of the 31 who were not suppressed, 10 increased to the 8-mg dose and four of these patients achieved testosterone suppression.

Leinung said there "didn't appear to be good correlation between the levels of estrogen in the blood and testosterone suppression."

Medroxyprogesterone was used on top of estradiol in 32 patients in order to achieve testosterone suppression, but only 31% of these patients overall did so: 25% of those using 4 mg estradiol, 32% of those on 6 mg estradiol, and 33% of those taking 8 mg of estradiol.

Overall, 50% of patients had suppressed testosterone at the last visit, spanning all doses and occurring with or without the use of a progestin, Leinung said.

He noted that spironolactone didn't lower testosterone levels, and there was actually a trend toward higher levels with the anti-androgen; it was a similar case for finasteride, which was associated with higher testosterone levels while on estrogen.

Leinung concluded that while estradiol can increase estrogen levels, it isn't completely effective in suppressing testosterone levels in male-to-female transgender patients. Adding a progestin can aid with further suppression, but many patients remain incompletely suppressed, he said.

The presentation that followed Leinung's, however, discussed a study that had somewhat different results.

Lindsey Spratt, MD, of Maine Medical Center in Portland, and colleagues reported that all 12 of the male-to-female patients they saw at their clinic achieved levels of testosterone within the normal range for an adult female (1.1 to 6.3 pg/mL) by using estradiol doses of 4 to 10 mg/day with spironolactone 100 to 200 mg/day.

Spratt said her findings suggest that most transgender patients may not need additional agents beyond estrogen therapy to suppress endogenous gonadal activity, and that it should be assessed alone "before adding additional endocrine therapies to suppress ovarian or testicular activity to avoid unnecessary expense or side effects."

Joshua Safer, MD, of Boston University, said Leinung's presentation provides "very useful data where we have so little," but was concerned about that group's spironolactone findings.

"It's counter to what a lot of us believe," Safer said during the presentation. "Perhaps it is due to a smaller sample size or selection bias."