In the Journals

Estrogen plus spironolactone therapy not associated with prolactin levels in transgender women

Joshua D. Safer, MD
Joshua D. Safer

Transgender women on a long-term regimen of estrogen and spironolactone therapy did not experience a clinically relevant change in prolactin level, suggesting the therapy combination is safe in this population, according to findings from a retrospective study published in Endocrine Practice.

The data suggest that it may be unnecessary to monitor prolactin in patients receiving estrogen therapy, Joshua D. Safer, MD, executive director of the Mount Sinai Center for Transgender Medicine and Surgery at the Icahn School of Medicine at Mount Sinai, told Endocrine Today.

“It is standard in many of the transgender guidelines to recommend that prolactin is monitored,” Safer said. “The observation among clinicians, though, is that they check these prolactin levels and don’t find a lot. In every circumstance where I saw a patient with an elevated prolactin that was causing anxiety about their care, I went and proved with the patient that the elevated prolactin was not dependent on her estrogen dose and she stayed on her hormones. Anecdotally, I’ve never seen this be a big problem, so we looked at our patients systematically to see if it was true.”

Safer and colleagues retrospectively analyzed chart data from 98 transgender women receiving estrogen therapy, recruited between 2015 and 2016 from the endocrinology clinic at Boston Medical Center (mean age, 41 years; mean BMI, 28 kg/m²). Standard transfeminine hormone therapy at Boston Medical Center includes daily oral estradiol or conjugated estrogens, along with adjunctive spironolactone, with a goal of achieving a serum testosterone level less than 100 ng/dL. Patients were regularly monitored for elevated prolactin levels per Endocrine Society guidelines. Researchers analyzed levels of estradiol, testosterone and prolactin, BMI and spironolactone dosage. Patients were examined at 3-month intervals for the first year of therapy and at 6-month intervals thereafter, although not all patients had recorded laboratory values for all measures at all visits. Researchers conducted bivariate analyses on estradiol, testosterone, BMI, patient age and spironolactone dosage vs. prolactin levels to determine the existence of any relationship between those factors.

Within the cohort, 79% of patients were on oral estradiol, 19% were on conjugated estrogens and 2.5% received transdermal estradiol. Average dose of spironolactone was 161 mg, and average dose of estradiol was 3.1 mg.

During 6 years of follow-up, researchers observed no statistically significant rise in prolactin levels in the cohort.

The researchers observed several prolactin elevations, despite an absence of symptoms, they noted. Among those individuals, all underwent pituitary evaluation and had prolactin levels measured while off estrogen. No pituitary disease was diagnosed in these patients, according to researchers. Additionally, over 6 years, no patients were diagnosed with a prolactinoma. Across a broad range of estradiol levels, testosterone levels and spironolactone dosages, researchers observed no significant association with serum prolactin levels.

“We propose that there is no significant rise in prolactin when transgender women are treated with spironolactone as the adjunct anti-androgen, and that it is not necessary to monitor prolactin in women on this treatment combination,” the researchers wrote.

The study is the first to examine a relatively large cohort of transgender women with data over an extended period, and the data suggest that physiologic-level estrogen therapy for transgender women does not induce prolactinomas or hyperprolactinemia, Safer said.

“The next steps are for my former group and others around the country to put together more rigorous projects,” Safer said. “We need to think about funding for cohorts to look at larger sample sizes, for this and other things that people assume to be true with transgender people that are not true and to discover things that may be generally concerning, but where we have no knowledge.

“This is one lab test that seems to be unnecessary,” Safer said. – – by Regina Schaffer

For more information:

Joshua D. Safer, MD, can be reached at can be reached at the BMC Center for Transgender Medicine and Surgery, 1 Boston Medical Center Place Boston, MA 02118; email: jsafer@bu.edu.

Disclosures: The authors report no relevant financial disclosures.

Joshua D. Safer, MD
Joshua D. Safer

Transgender women on a long-term regimen of estrogen and spironolactone therapy did not experience a clinically relevant change in prolactin level, suggesting the therapy combination is safe in this population, according to findings from a retrospective study published in Endocrine Practice.

The data suggest that it may be unnecessary to monitor prolactin in patients receiving estrogen therapy, Joshua D. Safer, MD, executive director of the Mount Sinai Center for Transgender Medicine and Surgery at the Icahn School of Medicine at Mount Sinai, told Endocrine Today.

“It is standard in many of the transgender guidelines to recommend that prolactin is monitored,” Safer said. “The observation among clinicians, though, is that they check these prolactin levels and don’t find a lot. In every circumstance where I saw a patient with an elevated prolactin that was causing anxiety about their care, I went and proved with the patient that the elevated prolactin was not dependent on her estrogen dose and she stayed on her hormones. Anecdotally, I’ve never seen this be a big problem, so we looked at our patients systematically to see if it was true.”

Safer and colleagues retrospectively analyzed chart data from 98 transgender women receiving estrogen therapy, recruited between 2015 and 2016 from the endocrinology clinic at Boston Medical Center (mean age, 41 years; mean BMI, 28 kg/m²). Standard transfeminine hormone therapy at Boston Medical Center includes daily oral estradiol or conjugated estrogens, along with adjunctive spironolactone, with a goal of achieving a serum testosterone level less than 100 ng/dL. Patients were regularly monitored for elevated prolactin levels per Endocrine Society guidelines. Researchers analyzed levels of estradiol, testosterone and prolactin, BMI and spironolactone dosage. Patients were examined at 3-month intervals for the first year of therapy and at 6-month intervals thereafter, although not all patients had recorded laboratory values for all measures at all visits. Researchers conducted bivariate analyses on estradiol, testosterone, BMI, patient age and spironolactone dosage vs. prolactin levels to determine the existence of any relationship between those factors.

Within the cohort, 79% of patients were on oral estradiol, 19% were on conjugated estrogens and 2.5% received transdermal estradiol. Average dose of spironolactone was 161 mg, and average dose of estradiol was 3.1 mg.

During 6 years of follow-up, researchers observed no statistically significant rise in prolactin levels in the cohort.

The researchers observed several prolactin elevations, despite an absence of symptoms, they noted. Among those individuals, all underwent pituitary evaluation and had prolactin levels measured while off estrogen. No pituitary disease was diagnosed in these patients, according to researchers. Additionally, over 6 years, no patients were diagnosed with a prolactinoma. Across a broad range of estradiol levels, testosterone levels and spironolactone dosages, researchers observed no significant association with serum prolactin levels.

“We propose that there is no significant rise in prolactin when transgender women are treated with spironolactone as the adjunct anti-androgen, and that it is not necessary to monitor prolactin in women on this treatment combination,” the researchers wrote.

The study is the first to examine a relatively large cohort of transgender women with data over an extended period, and the data suggest that physiologic-level estrogen therapy for transgender women does not induce prolactinomas or hyperprolactinemia, Safer said.

“The next steps are for my former group and others around the country to put together more rigorous projects,” Safer said. “We need to think about funding for cohorts to look at larger sample sizes, for this and other things that people assume to be true with transgender people that are not true and to discover things that may be generally concerning, but where we have no knowledge.

“This is one lab test that seems to be unnecessary,” Safer said. – – by Regina Schaffer

For more information:

Joshua D. Safer, MD, can be reached at can be reached at the BMC Center for Transgender Medicine and Surgery, 1 Boston Medical Center Place Boston, MA 02118; email: jsafer@bu.edu.

Disclosures: The authors report no relevant financial disclosures.