Childhood oestrogen may normalise thelarche in Turner syndrome

By Eleanor McDermid, Senior medwireNews Reporter

Treating girls with Turner syndrome with low-dose oestrogen from childhood results in earlier thelarche and a slower tempo of puberty, research shows.

The analysis involved 123 girls with Turner syndrome who participated in a large randomised trial, in which they received childhood oestrogen or placebo, with or without growth hormone. The 61 girls assigned to receive oestrogen (oral ethinyl estradiol) took a dose of 25 ng/kg per day from the ages of 5 until 8 years old, rising to 50 ng/kg per day from the age of 8 years. All study participants received 100 ng/kg per day from the age of 12 years (pubertal induction phase).

Girls given childhood oestrogen reached thelarche (sustained Tanner breast stage ≥2) significantly earlier than the 62 girls given placebo, at a median of 11.6 versus 12.6 years of age, but both groups reached subsequent pubertal milestones at the same age. Thus, the time between thelarche and menarche, at age 15.0 years in both groups, was significantly longer in girls given childhood oestrogen, at 3.3 versus 2.6 years in placebo-treated girls.

There were no differences between the groups before the age of 8.5 years, showing that the 25 ng/kg per day dose did not induce pubertal changes. Researcher Charmian Quigley (Indiana University School of Medicine, Indianapolis, USA) and co-workers note that the childhood oestrogen regimen “was not intended to induce feminization”. However, around half of the girls receiving childhood oestrogen attained thelarche before pubertal induction commenced, compared with about a quarter of those in the placebo group.

“While this finding might be interpreted as rationale for maintaining the 25ng/kg/d dosage until age 12, we propose that the general principle of increasing the estrogen dosage at around age 8 remains physiologically appropriate, as long as breast and bone maturation are carefully monitored and such increases are carefully individualized”, the researchers write in The Journal of Clinical Endocrinology & Metabolism.

Fifty percent of girls in the placebo group received a dose reduction at some point during the study, as did 62% of those taking childhood oestrogen. The difference was only significant during the second phase (age 8 until 12 years), at 31% versus 54%, with the most common reason being premature breast development.

But the team comments that the quarter of girls who achieved thelarche before pubertal induction did so in line with the typical age for White US girls, noting that this near normalisation “may have psychosocial benefits”.

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