SAN FRANCISCO – Hormonal therapies for transgender patients that block puberty and/or deliver opposite-sex hormones did not adversely affect bone development in adolescents and caused no serious side effects in teens or adults, two studies found.
The separate European studies, presented at the Endocrine Society Annual Meeting, looked at 127 adolescents aged 12-18 years in one study and 104 adults in the other study who were followed for 1 year after starting hormonal therapy.
The adolescents started gonadotropin-releasing hormone analogues (GnRHa) at ages 12-16 years to block production of sex hormones that initiate puberty, and at age 16 years they began receiving cross-sex hormones (either estrogen or testosterone) to induce sexual characteristics of the opposite sex to which they were transitioning. Adolescence is a key period for developing bone mass, so investigators followed patients’ bone density and other measures to see if there were any long-term adverse effects.
Dr. Henriette Delemarre-van de Waal
All patients had normal whole-body and hip-bone mineral density before hormonal therapy started. Bone density gradually increased in younger patients during GnRHa treatment, but less than would be expected without GnRHa. In patients who started GnRHa at relatively older ages, bone density decreased slightly, but both groups caught up to normal or near-normal bone density once they got cross-sex hormones and developed physiologic puberty. Patients who started the medical intervention with GnRHa at a young age and, thus, an early pubertal stage, showed the best bone density, reported Dr. Henriette Delemarre-van de Waal and her associates.
"The medical intervention in young transsexuals appears to be safe and effective," said Dr. Delemarre-van de Waal, professor of pediatric endocrinology at Leiden (Netherlands) University.
Patients reported satisfaction and no regrets about GnRHa therapy, but many commented that they would have liked to take cross-sex hormones earlier than age 16, she added at a press briefing on her study. Current Dutch law and Endocrine Society guidelines for treating transgender persons, which Dr. Delemarre-van de Waal helped develop, recommend waiting until age 16 to start cross-sex hormones. Efforts are underway to talk with the Dutch government about lowering the starting age of cross-sex hormonal therapy for selected patients, she said in an interview. Puberty in European girls starts at 10-11 years of age, so starting GnRHa before age 12 and cross-sex hormones before age 16 might optimize bone mass development, "but I think we need a little more data," she said.
Neither lipid levels nor insulin sensitivity per Tanner stage were adversely affected by puberty suppression or cross-sex hormones. GnRHa therapy delayed growth not only in bone age but in height, which was a concern especially for female-to-male transitioning patients who hoped to achieve the average taller height of males. Individualizing the addition of the anabolic steroid oxandrolone to cross-sex therapy helped achieve appropriate height in these patients, and estrogen therapy in male-to-female transgender patients suppressed growth velocity in height as desired by those patients.
A separate ongoing, prospective study analyzed data from four established gender-treatment teams in Belgium, the Netherlands, Norway, and Italy on 104 transgender adults in order to increase the limited knowledge about side effects from hormonal therapy. Females transitioning to males received standardized treatment with intramuscular testosterone undecanoate for 12 weeks. Males transitioning to females who were 45 years of age or younger were treated with standardized regimens of cyproterone acetate and estradiol valerate. Older male-to-female transsexuals received cyproterone acetate and a transdermal estradiol patch.
A year after starting therapy, no patients had developed adverse events serious enough to stop therapy, reported Dr. Katrien Wierckx of Ghent (Belgium) University and her associates. There were no deaths, cardiovascular events, osteoporotic fractures, venous thrombosis, pulmonary embolism, or prolactinomas.
Female-to-male transmen reported a significant increase in sex drive, voice instability, and androgenetic alopecia. Investigators observed significant increases in acne scores and total body lean mass, lower total body fat mass, and development of a less favorable lipid profile with lower high-density lipoprotein (HDL) levels and higher triglyceride levels, Dr. Wierckx said.
Male-to-female transwomen reported a significant decrease in sex drive and significant increases in breast tenderness, emotionality, and hot flashes. The hot flashes surprised investigators because this side effect had not been reported in previous studies. Measurements showed significant gains in fat mass, losses in muscle mass, and decreased insulin sensitivity. They developed a more favorable lipid profile with significantly reduced levels of total and low-density lipoprotein (LDL) cholesterol and triglycerides.
The findings suggest that current treatment regimens for transsexual women and men carry a low risk for short-term adverse events, Dr. Wierckx said. "These results are somewhat in contrast with most previously published studies, which observed a high incidence of venous thrombosis or pulmonary embolism during the first year of treatment," she said. This may suggest that treatment regimens avoiding the use of high-dose estradiol and high-dose cyproterone acetate have less detrimental effects on the coagulation system, she suggested.