75% of Transgender Women Fail to Suppress Testosterone

Becky McCall

March 01, 2018

Only one quarter of transgender women who received spironolactone for testosterone suppression achieved testosterone levels considered within the usual female range, according to results of a new single-center, cross-sectional study.

Patients in the other three quartiles did not achieve testosterone levels considered to be within the usual female physiologic range (serum testosterone < 50 ng/dL), as indicated by the Endocrine Society guidelines for transgender women.

Published in the February issue of Endocrine Practice (2018;24:135-142), this is the first study to show that the US medical regimen of spironolactone (100–200 mg/day) with estradiol can lower testosterone levels in some transgender women to within the usual female range, in an effort to align physical appearance with gender identity.

The authors, led by Jennifer J Liang, MS, from Boston University School of Medicine, Massachusetts, write that "identification of reasons why certain patients have better testosterone suppression could help improve antiandrogen therapy and allow for targeted interventions to advance the US medical regimen for transgender women."

Efficacy of Testosterone Suppression Has Not Been Evaluated

A goal of transgender medical intervention for many transgender individuals is to align physical appearance with gender identity. The strategy for transgender women (male to female) includes medication and/or surgery to decrease testosterone levels to the female range. Most transgender women depend on medical treatment alone to lower their testosterone levels, and in the United States, spironolactone is the primary adjunctive antiandrogen used for this purpose.

Hormone therapy in transgender adults is considered safe, however, the efficacy of treatment for testosterone suppression with medical treatment alone has not been evaluated. This study aimed to assess testosterone suppression using a regimen of spironolactone and estrogens.

Testosterone and estradiol levels were taken from the electronic medical records of 98 transgender women treated with oral spironolactone and estrogen at the endocrinology clinic at Boston Medical Center.

The therapeutic goal was to achieve serum testosterone levels below 100 ng/dL without estradiol becoming supra-physiologic (maintaining estradiol levels below 200 pg/mL). Both estrogen and spironolactone were titrated to achieve the goal.

Testosterone levels from therapy initiation through 3.5 years were recorded and patient data were aggregated into quartiles based on average steady-state testosterone levels. Quartile one represented the best testosterone suppression and quartile four represented the worst.

Patients were also aggregated into normal weight, overweight, and obese based on their average body mass index (BMI) across the study. People with normal BMI started at significantly higher testosterone levels than obese individuals.

Participants were also grouped according to their average spironolactone dosage and age. Estradiol levels were assessed relative to testosterone.

Is Success Down to Adherence?

Overall, the median testosterone levels of transgender women declined from 385 ng/dL at the initial visit to consistently under 130 ng/dL by 12 months.

Baseline average testosterone level was not a useful predictor of patient response to testosterone suppression strategies, the researchers note. This suggests that testosterone level at the initial clinical visit is not a reliable indicator of whether the patient will achieve success with treatment.

The highest suppression quartile achieved a mean testosterone level of 27 ng/dL. The second highest quartile did not achieve testosterone levels in the female range, but remained below the male range almost all the time. The least suppressed quartile was unable to achieve any significant testosterone suppression.

Participants with normal BMI showed the steepest decline in testosterone over the 9 months (average time to reach steady state) but did not reach the female range overall. 

Those with BMI in the obese range at baseline showed the least steep decline but seemed able to achieve the lowest levels of testosterone overall, note the authors. By 18 months, there was significant overlap among all categories.

The researchers add that age was not a useful predictor of success with testosterone suppression. Patients in all spironolactone dosage quartiles followed a similar pattern of decline in mean testosterone. Serum estradiol levels did not change over time or correlate with estradiol dose administered.

Discussing the findings, Liang and colleagues note that, of participants in the quartile unable to achieve any significant testosterone suppression, they may have had difficulty adhering to treatment or had a different physiologic response to treatment than others.

"On the other hand, patients who were able to achieve high levels of suppression may have adhered stringently to their treatment or had a robust response based on physiology."

Endocr Pract. 2018;24:135-142. Abstract

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