NEW YORK (Reuters Health) – Sex-hormone treatment in transgender individuals has complex sex-specific effects on body composition and metabolic cytokine secretion, researchers from Germany report.
Transgender individuals typically undergo gender-affirming hormonal therapy (GAHT) and gender-affirming surgeries to mitigate feelings of gender dysphoria. GAHT has been shown to affect circulating levels of cytokines, but the underlying mechanisms and consequences are poorly understood.
Dr. Matthias K. Auer from Max Planck Institute of Psychiatry and Klinikum der Ludwig-Maximilians-Universitaet, in Munich, Germany, and colleagues investigated several metabolic cytokines and their impact on the metabolic phenotype of 69 transgender individuals (24 transwomen and 45 transmen) before and 12 months after initiating GAHT.
Transwomen experienced increases in fat mass with consistent lean mass, whereas transmen showed decreases in fat mass and increases in lean mass, the researchers report in The Journal of Clinical Endocrinology & Metabolism, online December 5.
Adiponectin levels increased in transwomen, but strongly decreased in transmen. Chemerin and progranulin levels decreased in both sexes, whereas resistin and adipocyte fatty acid-binding protein (AFABP) levels did not change in either sex.
Fibroblast growth factor 21 (FGF-21) concentrations decreased in transwomen but remained unchanged in transmen.
Decreased triglyceride levels in transwomen were best explained by decreases in fat mass and increases in FGF-21, whereas their decreases in total and LDL cholesterol levels were mainly related to their consistently lower resistin levels.
In transmen, on the other hand, increases in LDL-cholesterol were linked to decreases in FGF-21, whereas decreases in the HDL/total cholesterol ratio were related to declines in adiponectin levels.
Changes in cytokines did not predict worsening insulin resistance in transwomen, but improving hepatic insulin sensitivity in transmen was positively associated with chemerin, resistin and FGF-21 levels and inversely associated with changes in leptin and AFABG levels.
“One of the most in-depth analyses to date has, in this study, succeeded in further disentangling the direct and indirect effects of GAHT on components of the metabolic syndrome in transgender individuals,” the researchers conclude. “Many effects of GAHT on components of the metabolic syndrome seem to be directly attributable to changes in the sex steroid milieu; however, there are also indirect sex-specific effects involving mediators, such as changes in body composition and metabolic cytokine secretion, or a combination of both these factors.”
Dr. Deborah J. Clegg from Cedars-Sinai Medical Center in Los Angeles, California, who recently reviewed the metabolic impact of cross-hormone therapy, told Reuters Health by email, “So much has not been known about the metabolic impact of cross-hormone therapy. This paper, as well as several others recently published, is beginning to shed some light on this. It would be fabulous if the study were powered with more subjects, to eventually allow for drug/treatment recommendations to be generated. At the moment, the clinician would not have a ‘take-home message’ from this study – we would need to look at differing amounts and types of cross-hormone therapy in order to change current clinical practice.”
“This study begins to alert the clinician to monitor these adipocytokines, blood pressure, and insulin sensitivity in this at-risk population,” said Dr. Clegg, who was not involved in the research.
“It is unclear to me if the transwomen in this study had gender-affirming surgery – meaning, did they still have testes or had they elected for the orchiectomy?” Dr. Clegg added. “In our study population, this made a huge difference in metabolic outcome measurements – and it would be interesting to see if they had enough power to separate those individuals who did and did not have surgery.”
Dr. Roberto Vita from the University of Messina in Italy, who was not involved in the study, has also studied changes in hormonal and metabolic parameters in transgender individuals on cross-hormone therapy. He told Reuters Health by email, “The most interesting aspect of this prospective study is that metabolic changes ensuing cross-sex-hormone therapy depend not only on the therapy per se, but also on the effects that it has on cytokines with ‘metabolic’ actions.”
“This study reinforces the need to monitor metabolic parameters in transgender people,” he said. “Management of transgender persons on hormone therapy needs endocrinological supervision.”
Dr. Auer did not respond to a request for comments.
SOURCE: http://bit.ly/2kWT5rW
J Clin Endocrinol Metab 2017.
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