(Boston)--The majority of transgender women who follow the usual approach prescribed in the United States are unable to reliably lower their testosterone levels into the typical female physiologic range with medicine alone.

The study, which appears in the journal Endocrine Practice, is the first to investigate the efficacy of transgender treatment in terms of achieving targeted and subsequent stability of testosterone levels achieving over a prolonged period of several years.

Transgender individuals are those with gender identity different from external sexual anatomy at birth. Recent studies report that 0.6 percent of the adult population in the U.S. identify as transgender. A goal of transgender medical intervention is to align physical appearance with gender identity. The strategy for transgender women (male-to-female) includes medication and/or surgery to decrease or suppress testosterone levels into the female range. Most transgender women depend on medical treatment alone to lower their testosterone levels.

The researchers extracted testosterone and estradiol levels from the electronic medical records of 98 anonymized transgender women treated with oral spironolactone and oral estrogen therapy. Patients were separated into four similarly sized groups using the average estradiol dose they were administered over the course of their treatment. The Endocrine Society guidelines on monitoring transgender women suggests that patients should reach a serum testosterone <50ng/dl.

Only a quarter of transgender women taking a regimen of spironolactone and estrogens were able to lower testosterone levels within the usual female physiologic range. Another quarter could not achieve female levels but remained below the male range virtually all of the time, while one quarter was unable to achieve any significant suppression.

"This study allowed us to identify patients who achieved differing levels of testosterone suppression, including a group of patients unable to achieve any significant testosterone suppression. These patients may have had difficulty adhering to their treatment or may have had a different physiologic response to treatment than other patients. On the other hand, patients who were able to achieve high levels of suppression may have adhered stringently to their treatment or had robust response based on physiology," explained corresponding author Joshua D. Safer, MD, FACP, associate professor of medicine at Boston University School of Medicine.

"Also, it is not known if there is an absolute need for all transgender women to suppress the testosterone levels entirely into the female range. Perhaps it is acceptable for some to have levels just above the usual female upper limit."

The researchers believe future studies could pinpoint specific characteristics of patients who fall into each quartile of average steady state testosterone. "Identification of reasons why certain patients have better testosterone suppression could help improve anti-androgen therapy and allow for targeted interventions to advance the U.S. medical regimen for transgender women. As well, future study could determine the specific impact of testosterone at different levels even if not entirely in the female range," said Safer, also the Medical Director of the Center for Transgender Medicine and Surgery at Boston Medical Center.

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