Assessing the value of treatments to increase height

(Press-News.org) CLEVELAND -- Dr. Leona Cuttler, a pediatric endocrinologist and growth hormone expert from University Hospitals Rainbow Babies and Children's Hospital, is the co-author of an editorial in the New England Journal of Medicine commenting on a new study that found giving girls with Turner syndrome low doses of estrogen, as well as growth hormone, years before the onset of puberty, increases their height and offers other benefits.

With her co-author Dr. Robert L. Rosenfield, a pediatric endocrinologist with the University of Chicago Medical Center, Dr. Cuttler writes, "The use of growth hormone and estrogen has a long and often controversial history in the manipulation of growth."

About the new study, they write that the results confirm those of previous, less rigorous studies showing that treatment with growth hormone significantly increased adult height in patients with Turner's syndrome.

Drs. Cuttler and Rosenfield say the results suggest a modest but intriguing synergism between growth hormone and low-dose estrogen in promoting growth.

"The impact of these findings on practice and policy will depend not only on their statistical significance but also on whether the observed changes in height translate into clinically meaningful benefit. The ability to increase height should not be the sole yardstick for assessing benefit," the editorial states.

"Since growth hormone is well entrenched in the management of Turner's syndrome, the current findings support this aspect of practice but are not likely to change it. Yet the results underscore the need for a measured approach, which includes avoiding unrealistic expectations, when families embark on growth hormone therapy. The early use of low-dose estrogen in conjunction with growth hormone is an interesting possibility. An optimal estrogen-replacement regimen could potentially shorten the period of growth hormone treatment, reduce costs, and improve patient satisfaction. However, implementation would be hampered by the lack of a convenient means to deliver the very small estrogen doses that seem to be optimal for height augmentation."

The authors advise caution when considering supplementing growth hormone treatment with early, low-dose estrogen in Turner's syndrome. "The current results show trends that do not consistently reach significance and show only modest synergy between growth hormone and estrogen in achieving height augmentation, as compared with growth hormone alone. The suggested potential benefits of estrogen on cognition are based on earlier short-term data, and long-term data are needed. We must be concerned about unexpected risks posed by estrogen, being mindful of surprising adverse outcomes of estrogen use in other settings," they write.

According to the National Institutes of Health, Turner syndrome occurs in 1 out of 2,500 female births worldwide and develops when a female (X) sex chromosome is missing in cells or is abnormal. These girls are typically of short stature and have a loss of ovarian function.

### Dr. Cuttler directs the Center for Child Health and Policy and the Division of Pediatric Endocrinology, Diabetes, and Metabolism at UH Rainbow Babies and Children's Hospital and is on the faculty of the Case Western Reserve University School of Medicine. Dr. Rosenfield is in the Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, University of Chicago Medical Center.