medwireNews: The third-generation aromatase inhibitor (AI) letrozole slows skeletal maturation and improves adult height in girls with McCune–Albright syndrome (MAS) and gonadotropin-independent precocious puberty, a long-term study shows.

“This study is the first to report adult height for any intervention in girls with MAS”, say Alison Boyce (National Institutes of Health, Bethesda, Maryland, USA) and co-researchers.

The 28 girls in the study received letrozole treatment for an average of 4.1 years, with follow-up for an average of 6.0 years. The average pretreatment predicted adult height Z-score in 18 girls with this information was –2.9; this improved to –0.8 during treatment. The four patients who achieved their final adult height had mid-parental height Z-scores ranging from –0.3 to +1.1.

“Despite the small subject numbers, letrozole treatment resulted in a statistically significant increase in adult height, further supporting the efficacy of this therapy”, write the researchers in the European Journal of Endocrinology.

By comparison, a group of 42 untreated historical controls achieved an average adult height Z-score of just –3.0, and 14 with available data achieved a mid-parental height Z-score of –3.5. A further group of 20 untreated MAS patients without precocious puberty achieved normal adult and mid-parental heights.

The ratio of change in bone age to change in chronological age was increased prior to letrozole treatment, at 1.7, but this decreased significantly during treatment, to 0.5. Likewise, growth velocity Z-scores fell from 2.2 to –0.6.

“These findings demonstrate that unlike previous studies in other AI formulations, the third-generation AI letrozole is an effective treatment for MAS-associated [precocious puberty]”, says the team.

Patients also experienced a reduction in the frequency of vaginal bleeding while on treatment, as well as stabilisation of breast and pubic hair development and a reduction in their oestradiol levels.

Five patients entered central puberty during treatment, at an average chronological age of 8.9 years and bone age of 11.5 years. Three were treated with gonadotropin-releasing hormone analogues, with puberty allowed to continue in the fifth, who was 12.3 years of age.

Of note, the patients on letrozole therapy had no significant differences between pre- and on-treatment uterine or ovarian volumes.

“Letrozole is therefore the only available treatment for MAS-associated [precocious puberty] that demonstrates long-term efficacy without stimulatory effects on the uterus”, say Boyce and team. One patient discontinued letrozole when she developed ovarian torsion, but they note that this was as likely to be associated with the disease as with its treatment.

By Eleanor McDermid

Eur J Endocrinol 2016; Advance online publication

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