In Transgender Youth, Obesity Impacts Effects of Sex Steroids on HDL-C

By Marilynn Larkin

February 25, 2021

NEW YORK (Reuters Health) - In transgender and gender-diverse young people receiving sex steroids, obesity exacerbates the decrease in high-density lipoprotein cholesterol (HDL-C) levels and attenuates the benefits of estradiol, researchers say.

"This study adds to what is known about the role of sex steroids (i.e., estrogen and testosterone) in cholesterol metabolism," Dr. Kate Millington of the Ann and Robert H. Lurie Children's Hospital in Chicago told Reuters Health by email. "Understanding how sex steroids impact cholesterol changes has implications for men and women and for individuals at times of transition, such as puberty and menopause."

Dr. Millington and colleagues collected data on 269 transgender and gender-diverse young people at baseline and at six and 12 months after beginning gender-affirming hormones (GAH), according to the research letter published in JAMA Pediatrics.

Eighty-three participants (31%) were designated male at birth (DMAB); the rest were designated female at birth (DFAB).

After six months of estradiol treatment, mean HDL-C levels increased in DMAB participants by 11.2 mg/dL, falling within the range for female adolescents. Similarly, after six months of testosterone treatment, HDL-C levels in DFAB participants decreased by a mean of 7.2 mg/dL, falling to a level nearly identical to that of DMAB participants at baseline.

Obesity attenuated the benefit of estradiol treatment on HDL-C levels and exacerbated the association of testosterone treatment with outcomes after six months.

Obese DMAB participants had lower HDL-C levels at baseline than non-obese DMAB participants (mean, 36.0 mg/dL vs. 46.1); they also demonstrated a nonsignificant change in HDL-C levels with estradiol (mean, 36.0 mg/dL vs. 41.3 mg/dL).

Although baseline HDL-C levels were not significantly different between obese and non-obese DFAB participants, (mean, 48.9 mg/dL vs. 53.5 mg/dL), the fall in HDL-C levels with testosterone was more pronounced in those who were obese (mean, −12.1 mg/dL vs. −5.5 mg/dL).

Additional analyses showed that GAH-induced HDL-C changes remained consistent, regardless of age, race, and tobacco use.

Further, GAH treatment did not induce significant changes in low-density lipoprotein cholesterol or triglyceride levels.

Dr. Joshua Safer, Executive Director of the Mount Sinai Center for Transgender Medicine and Surgery and Professor of Medicine at the Icahn School of Medicine at Mount Sinai in New York City, commented by email to Reuters Health. "The data are some of the clearest to date that suggest an inverse relationship between testosterone levels and HDL cholesterol levels. Unfortunately, the paper does not report the hormone levels which would be needed to confirm the reported association."

"A notable finding is that obese youth had worse HDL cholesterol levels in all cases," he said.

"The data suggest that higher testosterone levels can play an important part in worsening cholesterol profiles," he said. "However, worse cholesterol profiles can be true for anyone with obesity, regardless of their hormone levels."

SOURCE: https://bit.ly/37I2VHu JAMA Pediatrics, online February 15, 2021.

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