Estrogen plus GH increases height for girls with Turner’s syndrome

Giving girls with Turner’s syndrome low-dose estrogen in combination with growth hormone years before the onset of puberty appears to increase adult height.

In addition, combining childhood ultra-low-dose estrogen with GH may provide other benefits associated with early initiation of estrogen replacement, Judith Ross, MD, and colleagues wrote in The New England Journal of Medicine.

Results of a decades-long study that took more than 20 years to complete may change the practice of treating girls with Turner’s syndrome, Ross said in a press release.

“Our goal is to improve the health and lives of girls and women with Turner’s syndrome or with disorders that interrupt normal ovarian function,” she said in the release. “This study shows that our strategy accomplishes that.”

Beneficial effects of combination treatment

The current treatment standard for most girls with Turner’s syndrome is estrogen therapy at the onset of puberty. Recombinant human GH is commonly used to treat short stature associated with the syndrome. However, researchers wanted to determine whether there was additional benefit when childhood ultra-low-dose estrogen was combined with GH therapy in young girls.

Their study included 149 girls with Turner’s syndrome, aged 5 to 12 years, who were treated at Thomas Jefferson University Hospital or at the NIH between 1987 and 2003. Each girl was randomly assigned to one of four groups: placebo; GH alone; estrogen alone; or estrogen plus GH. The estrogen dose was one-fiftieth of the dose that girls would be given once they reached puberty, Ross said. GH was administered in 0.1 mg/kg of body weight three times per week. At the first visit after reaching age 12 years, girls in all groups received escalating doses of ethinyl estradiol, and GH was terminated once adult height was reached.

After an average study period of 7.2 years, mean SD scores for adult height were measured roughly 17 years later. According to the results, mean SD scores were: –2.81 for the placebo group; –3.35 for the estrogen only group; –2.29 for the GH only group; –2.1 for the GH plus estrogen group (P<.001).

GH was associated with a mean 0.78 SD score increase (5 cm) in adult height (P<.001). Further, girls who were assigned to the estrogen plus GH group had an adult height that was 0.32 SD score (2.1 cm) greater than girls assigned to GH alone (P=.059).

“It should be noted that adult height within the normal range was attained in 40% of GH-treated patients in this study, but in only 4% of non-GH-treated patients,” Ross said. “This research also shows that use of low-dose estrogen is synergistic with GH.”

In addition to its effects on height, estrogen and GH treatment also improved psychosocial and cognitive functioning.

Role of estrogen before puberty

According to Ross, “there is a place for estrogen replacement prior to puberty in girls who need it, and we have made the case that replacing it earlier in these children is very beneficial.”

In addition, the researchers said results of this study may also be of benefit for girls who have ovarian function that was damaged by chemotherapy or surgical removal or girls with other disorders.

For more information:

• Ross JL. N Engl J Med. 2011;364:1230-1242.

Disclosure: The study was funded by the National Institute of Child Health and Human Development and Eli Lilly and Company.

The study by Ross and colleagues is the culmination of a rigorous 23-year prospective study that assessed effects of GH and low-dose estradiol therapy on girls with Turner’s syndrome. Considering that GH therapy is universally applied in the treatment of girls with Turner’s syndrome, this study will represent the final chapter in the string of studies that conclusively show beneficial effects of GH on final height, although final adult heights remain about 2 SD below heights of those without Turner’s syndrome. Most intriguing, with low-dose estradiol in conjunction with GH long-term height gains without increasing adverse events. While supporting the notion that GH therapy is of benefit to girls with Turner’s syndrome, it shows that we can do even better with a small amount of estrogen.

– Scott A. Rivkees, MD

Chief of the Yale Pediatric Thyroid Center, Yale Child Health Research Center

Disclosure: Dr. Rivkees reports no relevant financial disclosures.

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