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Cross-sex HT not associated with surgical risk in transgender adults

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December 7, 2018

There is “insufficient evidence” to support the routine discontinuation of testosterone or spironolactone therapy in transgender patients who are undergoing scheduled surgical procedures, whereas inconsistent risk data regarding estrogen therapy suggests careful consideration about whether to stop before surgery, according to a systematic review published in JAMA Surgery.

Elizabeth R. Boskey

“There shouldn’t be a one-size-fits-all approach for how surgeons handle medication management for gender-diverse patients in the perioperative period,” Elizabeth R. Boskey, PhD, social worker and research fellow with the Center for Gender Surgery at Boston Children’s Hospital, told Endocrine Today. “Although research is limited, the data doesn’t support a need to discontinue testosterone or antiandrogens perioperatively. Studies on the perioperative risks of estrogens have been less clear, but suggest that rather than automatically discontinuing estrogen use, surgeons should weigh a variety of factors, including the type of surgery, the overall health of the patient and the possible risks of stopping treatment for the patient. It’s also important to consider the type of estrogen being used and the route of administration.”

Boskey and colleagues analyzed data from 18 studies assessing the effect of drugs used in cross-sex HT on perioperative risk, including 11 cohort studies, six case-control studies and one randomized controlled trial focusing on estrogens and progesterone (n = 12), spironolactone and antiandrogens (n = 4), testosterone (n = 1) and cross-sex HT (n = 1).

Data across studies were limited, according to researchers, but results suggest testosterone and spironolactone therapy are not associated with negative surgical outcomes. In one prospective study, researchers observed that transgender men taking testosterone were more likely to experience hematoma after chest surgery vs. those not taking testosterone at the time of surgery; however, the difference did not rise to significance. In a study of cisgender men undergoing cardiac surgery, researchers did not observe an increased risk for postoperative mortality, thrombosis or cardiovascular events in patients receiving preoperative testosterone (n = 947) vs. controls (n = 4,598).

In a study examining the use of spironolactone therapy, researchers observed no increased risk for atrial fibrillation after cardiac surgery for people taking the drug vs. those who were not. In another retrospective cohort study, 132 patients taking aldosterone agonists, including spironolactone, experienced a mean decrease in risk for atrial fibrillation vs. those who were not taking such medications, although the difference did not rise to significance, according to the researchers.

The researchers noted that data linking estrogen use and thrombosis is “inconsistent in the perioperative period” and does not address the types of estrogens that are used most often in cross-sex HT.

“More research is clearly needed on the perioperative risks of current hormone treatments used in gender-diverse patients,” Boskey said. “However, we also need better data on the risks — both physiological and psychological — of discontinuing cross-sex hormone treatment, even for a short time. That’s an underexplored area, which makes it difficult for surgeons to adequately assess the risks and benefits of discontinuing treatment.” – by Regina Schaffer

Disclosures: The authors report no relevant financial disclosures.

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It is common for transgender women to be advised to hold estrogen treatment for a number of weeks in the perioperative period when they are having surgeries. The strategy pays deference to a concern that exogenous estrogens might present an independent thrombosis risk during surgery. The Boskey review is reassuring in that the authors determined that the existing literature shows no such increased risk. Further, the authors observed that the studies that do show increased perioperative thrombotic events among any patients, including cisgender patients, primarily reflect a problem for users of ethinyl estradiol, specifically, in the form of oral contraceptives for cisgender women, rather than estrogens in general. Such a finding aligns with the observation among those treating transgender women that ethinyl estradiol is the primary thrombogenic agent identified to date. Indeed, the 2017 Endocrine Society guidelines already specifically recommend against the use of ethinyl estradiol to treat transgender women.

Although definitive, confirmatory research studies remain to be done, practitioners and their patients should walk away from the Boskey paper with two messages:  First, thinyl estradiol should be avoided when treating transgender women, and second, other than ethinyl estradiol, hormone regimens for transgender individuals are likely to be low risk, even if used throughout the perioperative period.

Joshua D. Safer, MD, FACP

Executive Director, Center for Transgender Medicine and Surgery,
Mount Sinai Health System,
Icahn School of Medicine at Mount Sinai

Disclosure: Safer reports no relevant financial disclosures.