Growing Taller With Turner Syndrome: What Families Should Know About Growth Hormone and Estrogen Treatment

Table of Contents

• Key Points
• Turner Syndrome and the Quest for Height
• The Landmark Trial Behind This Editorial
• Height Gains: The Key Numbers
• The Surprising Double Role of Estrogen
• Does Extra Height Improve Quality of Life?
• The Price of Every Extra Centimeter
• What This Means for Everyday Practice
• Safety Concerns: Why Caution Is Needed
• What Researchers Still Don't Know
• How Doctors Decide — and What Patients Should Ask
• Frequently Asked Questions
• Source Information

Key Points

• In a randomized placebo-controlled trial, growth hormone increased adult height in Turner syndrome by an average of 5.0 cm over 7 years.
• Adding low-dose estrogen in childhood tended to add about 1.7 cm, but this extra gain did not consistently reach statistical significance.
• Growth hormone for Turner syndrome was estimated to cost about $33,750–$35,000 (2010 dollars) per centimeter gained.
• In a French study, height achieved did not influence quality of life, social adjustment, or self-esteem in young women with Turner syndrome.
• Average adult height often remains below the normal range despite treatment, and individual height gains vary considerably.

Turner Syndrome and the Quest for Height

Turner syndrome (sometimes called Turner's syndrome) is a genetic condition that affects girls. It occurs when all or part of one of the two X chromosomes is missing or altered.

Its two medical hallmarks are short stature and hypogonadism (ovaries that fail to develop normally and therefore produce too little estrogen, the main female sex hormone). Because of both features, Turner syndrome has become a key testing ground for growth-promoting treatments.

The authors of this editorial begin with a historical observation. Growth hormone and estrogen have a long and often controversial record as tools to manipulate human growth.

Doctors have given growth hormone to make short children taller. They have also used high-dose estrogen deliberately to stifle growth in unusually tall girls. Today, drug treatments to increase growth in short children are increasingly common.

The authors state their core argument in the opening lines. The usefulness of any growth-promoting treatment depends on well-designed studies that measure two separate things: the actual effect on height, and the functional benefit of the height gained. In other words, what do those extra inches actually do for the patient's daily life and sense of well-being?

The Landmark Trial Behind This Editorial

This editorial comments on a unique study by Ross and colleagues, published in the same issue of the New England Journal of Medicine. That trial tested growth hormone treatment, given with or without early low-dose ethinyl estradiol (a potent, orally active synthetic form of estrogen), to see how the treatments affected adult height in Turner syndrome.

The trial was randomized and placebo-controlled. "Randomized" means the girls were assigned to their treatment group by chance. "Placebo-controlled" means some girls received an inactive dummy treatment, so researchers could compare the real drugs against no active medication.

The study began in 1987. Simply completing it was an achievement, given the regulatory changes that occurred along the way. These included a review by an expert panel of the ethics and safety of this study and a companion study, the Food and Drug Administration's (FDA's) approval of growth hormone for Turner syndrome in 1996, and shifts in recommended practice that made growth hormone treatment routine for patients with this condition.

The editorial notes that the findings confirm those of earlier, less rigorous studies. Treatment with growth hormone significantly increased adult height in patients with Turner syndrome.

Height Gains: The Key Numbers

The headline results, in numbers, are worth reading carefully. They show that growth hormone works, but it does not normalize height.

• Growth hormone versus placebo: Treatment produced a gain of 0.78 points in the adult-height standard-deviation score (a statistical measure of how far a person's height sits from the average for healthy girls of the same age). In everyday units, that is a significant gain of 5.0 cm (about 2 inches) over the 7-year study period.
• Growth hormone plus low-dose estrogen versus growth hormone alone: Starting the combination at an average age of 9.3 years tended to increase adult height further, by 0.26 standard-deviation points — roughly 1.7 cm (about two-thirds of an inch).
• Current higher-dose regimens: One study cited by the authors reported a gain of 7.2 cm (2.8 inches). Starting treatment even earlier in life might add more, the editorial notes, or both approaches combined could increase the gain.

Despite these gains, the average adult height of treated girls remained below the normal range. There was also considerable variation from one patient to another in how much height was gained.

Higher doses of growth hormone have not fully solved this problem. Even with such doses, the editorial states, average adult heights have been variable and, on average, still subnormal.

The Surprising Double Role of Estrogen

Estrogen is often thought of as the body's natural brake on growth. In fact, high-dose estrogen has been used for decades to reduce the adult height of very tall girls. Estrogen is both necessary for and sufficient to bring about epiphyseal closure (the process by which the growth plates at the ends of the long bones seal shut, ending further bone lengthening).

However, estrogen's effect on growth is biphasic (two-sided). High doses stop growth, but low doses increase height velocity (the speed at which a child grows per year). The body's own estradiol (the main natural estrogen) drives the normal female growth spurt during puberty. When provided at a physiologic dose (a dose that mimics normal body levels) and at the appropriate age, it stimulates the pubertal growth of teenage girls.

This creates a practical dilemma in Turner syndrome. Because doctors worried that estrogen would interfere with growth, common practice was to delay estrogen-replacement therapy until the mid-teens. But the editorial points out that this delay has downsides of its own. These include weaker bone mineral accrual (build-up of bone density) and delayed age-appropriate psychosocial development.

Importantly, prior research supports the idea that early, very low-dose estrogen is safe for growth. In a controlled study by Rosenfield and colleagues, low-dose estradiol given around the 12th year (intended to mimic the very low estrogen levels of early puberty) did not interfere with growth hormone's effects in Turner syndrome. It actually tended to increase growth and led to earlier attainment of adult height.

The data reported by Ross and colleagues are consistent with that earlier finding. The authors describe the apparent partnership between growth hormone and low-dose estrogen as a modest but intriguing synergism (a combined effect greater than either drug alone).

Does Extra Height Improve Quality of Life?

More height does not automatically mean a better life. That is one of the most important cautions in this editorial.

The authors argue that the ability to increase height should not be the sole yardstick for measuring benefit. For disorders in which final height would clearly be disabling, a gain of 5.0 to 7.5 cm may provide a practical benefit. But for others, the value of gained inches is less certain.

The editorial cites a study from France (the StaTur population-based cohort study) that examined young women with Turner syndrome who had been treated with growth hormone. In that study, achieved height did not influence quality of life, social adjustment, or self-esteem.

The authors recommend that reports of treatment effects on height include a systematic assessment of quality of life, functional status, and psychological adjustment. Only then, they argue, can patients and doctors understand what the documented height gains are actually worth.

The Price of Every Extra Centimeter

Height treatment carries a substantial price tag, and the editorial reviews the available economic data from the United Kingdom.

One analysis, from 2002, put the cost of growth hormone treatment for patients with Turner syndrome at £16,800 to £17,400 per centimeter of height gained. Adjusted to 2010 values, that is approximately £21,000 to £21,750, or $33,750 to $35,000, for each single centimeter (about 0.4 inches) of additional height.

A separate British analysis looked at cost-effectiveness in a different way. It calculated that the incremental cost of growth hormone treatment per quality-adjusted life-year gained — a quality-adjusted life-year (QALY) being a standard measure that combines both length and quality of life — was about £39,460 (approximately $61,565), as compared with no treatment.

These figures matter for policy. Even if growth hormone produces statistically significant height gains, the editorial argues, its value must be judged against these costs and against the real-world benefits patients experience.

What This Means for Everyday Practice

So how will the results affect the clinic? The editorial's answer is honest: growth hormone is already well entrenched in the management of Turner syndrome, so the current findings support this aspect of practice but are not likely to change it.

There is, however, a clear call for a measured approach. Families embarking on growth hormone therapy need help avoiding unrealistic expectations. The average gain is real but modest, and adult height often remains below the normal range.

The more interesting possibility raised by the trial is the early use of low-dose estrogen together with growth hormone. An optimal estrogen-replacement regimen could, in theory, shorten the period of growth hormone treatment, reduce costs, and improve patient satisfaction.

There is a practical obstacle, the authors note: doctors currently lack a convenient way to deliver the very small estrogen doses that appear optimal for height augmentation. Until such formulations exist, this approach will be hard to implement widely.

Safety Concerns: Why Caution Is Needed

Despite the promise of adding early low-dose estrogen to growth hormone, the editorial urges strong caution. The results show trends that do not consistently reach statistical significance. They also show only modest synergy with growth hormone in achieving height gain.

Some of the suggested benefits of estrogen — including possible effects on cognition — come from earlier short-term data. The authors state plainly that long-term data are needed before these benefits can be assumed.

History provides sobering warnings about estrogen's unexpected risks. The editorial reminds readers of two famous examples:

• Diethylstilbestrol (stilbestrol, a synthetic estrogen) was given to pregnant women in the mid-20th century. Decades later, their daughters were found to have a higher risk of vaginal adenocarcinoma (a rare cancer of the vagina).
• Postmenopausal women given oral estrogen-replacement therapy were later found to face a greater risk of cardiovascular disease (heart attack and stroke).

Even in the Ross study, the prepubertal doses of estradiol were very low — yet gynecologic disorders occurred frequently. These usually took the form of inappropriate feminization (breast development or vaginal bleeding occurring earlier than is typical for the patient's age).

The authors weigh two bone-related concerns side by side. By 12 years of age, bone mineral density in Turner syndrome is already affected by estrogen deficiency. Yet earlier-than-average pubertal feminization carries a slight risk of breast cancer, according to a study cited in the editorial.

There are also questions about the specific drug used. Ross and colleagues used ethinyl estradiol, a potent, orally active estradiol analogue. But routes of estrogen administration other than the oral route may change the outcomes, and other forms of estrogen may not behave identically to estradiol in the body.

What Researchers Still Don't Know

Many gaps remain in the evidence, and the editorial lists them explicitly. The optimal form, dosage, route of administration, and timing of estrogen-replacement therapy throughout the female life span have not yet been determined.

Every one of those variables could matter for both growth and long-term health. The oral estrogen pill used in the trial, for example, may act differently from estrogen delivered through the skin, and different estrogen molecules may have different effects in different tissues.

The editorial's message is that more research is needed — not just on height, but on the full balance of benefits, risks, and costs across a patient's lifetime.

How Doctors Decide — and What Patients Should Ask

In practice, doctors do not rely on growth charts alone. When deciding whether to recommend growth-promoting therapy, physicians take into account subjective factors — perceptions, beliefs, and attitudes — along with physiological data and scientific evidence. A national study of physician recommendations on growth hormone, published in Pediatrics in 2010, supports this view.

The authors conclude that the medical field needs to build knowledge systematically about two areas at once: the changes in height that treatments produce, and their potential value and functional benefit to patients. This combined knowledge is required, they say, to fully inform clinical decision-making and pharmacologic management for patients with Turner syndrome and other short-stature disorders.

For patients and families, this editorial suggests practical questions to bring to a doctor's appointment:

1. Ask about realistic expectations. On average, growth hormone adds about 5.0 cm over treatment periods of several years in Turner syndrome, but individual responses vary considerably. Average final height often remains below the normal range.
2. Ask how the height gain might translate into daily life. Evidence from France suggests that for many women with Turner syndrome, height does not determine quality of life, social adjustment, or self-esteem. Discuss what extra height would realistically mean for your child.
3. Ask about the timing and dose of estrogen. There is growing evidence that very low-dose estrogen, started early, does not harm growth hormone's effects — and may add about 1.7 cm. But ask about the frequent side effects, including early feminization, and the unresolved long-term questions.
4. Ask about cost. Growth hormone treatment for Turner syndrome was estimated to cost roughly $33,750 to $35,000 (in 2010 dollars) per centimeter of height gained. Cost-effectiveness data can inform shared decisions.
5. Ask what will be monitored beyond height. Bone density, psychosocial development, and quality of life deserve attention alongside the growth chart.

The editorial's closing message is clear. Height is one outcome — an important one — but it is not the whole story of successful treatment for Turner syndrome.

Frequently Asked Questions

What is Turner syndrome and why does it affect height?

Turner syndrome is a genetic condition in girls caused by a missing or altered X chromosome. It has two hallmarks: short stature and ovaries that fail to develop normally, producing too little estrogen. Growth hormone and estrogen treatments have been studied in Turner syndrome because these features directly affect growth and development.

How much height does growth hormone add for girls with Turner syndrome?

In a 7-year randomized placebo-controlled trial, growth hormone increased adult height by an average of 5.0 cm (about 2 inches) compared with placebo. The gain was statistically significant. However, individual responses varied, and average adult height still remained below the normal range for treated girls.

Does adding low-dose estrogen to growth hormone increase height further?

Starting low-dose estrogen around age 9.3 years along with growth hormone tended to add roughly 1.7 cm (about two-thirds of an inch) more than growth hormone alone. But this extra gain did not consistently reach statistical significance. Early low-dose estrogen may not interfere with growth hormone's effects.

What is the cost of growth hormone treatment for Turner syndrome?

One analysis estimated growth hormone treatment for Turner syndrome cost approximately $33,750 to $35,000 per centimeter of height gained, adjusted to 2010 dollars. A separate British analysis calculated about £39,460 per quality-adjusted life-year gained. These costs matter when judging whether height gains are worth the expense.

Does gaining extra height improve quality of life in Turner syndrome?

In a French study of young women with Turner syndrome who had received growth hormone, achieved height did not influence quality of life, social adjustment, or self-esteem. The editorial authors urge that reports on height effects should include quality-of-life and psychological assessments to understand what extra inches actually mean for patients.

What risks or side effects are associated with early low-dose estrogen and growth hormone?

In the trial, gynecologic disorders such as inappropriate feminization—breast development or vaginal bleeding earlier than typical—occurred frequently. The editorial stresses strong caution because trends did not consistently reach statistical significance, and long-term safety data on estrogen are still needed. Historical examples warn that estrogen can have unexpected risks.

What should families ask the doctor about height treatment for Turner syndrome?

Ask what realistic height gain to expect, since average gain is about 5.0 cm but varies. Ask how extra height might affect daily life and self-esteem. Ask about estrogen timing and dose, possible side effects like early feminization, costs, and what will be monitored beyond height, such as bone density and quality of life.

When should families seek a second opinion about growth hormone or early low-dose estrogen treatment for Turner syndrome?

Families considering growth hormone for Turner syndrome should consider a second opinion because average gain is modest—about 5.0 cm over 7 years—and adult height often stays below normal. Adding early low-dose estrogen may add only about 1.7 cm, with uncertain long-term safety and risk of early feminization. Treatment costs roughly $33,750 to $35,000 per centimeter gained in 2010 dollars, and height gain does not always improve quality of life. A second opinion can help weigh realistic expectations, safety questions, cost, and alternatives. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

This patient-friendly article is based on a peer-reviewed editorial published in the New England Journal of Medicine:

• Original title: Assessing the Value of Treatments to Increase Height
• Authors: Leona Cuttler, M.D., and Robert L. Rosenfield, M.D.
• Publication: N Engl J Med 2011; 364(13):1274–1276; published March 31, 2011.
• Companion research article discussed: Ross JL, Quigley CA, Cao D, et al. Growth hormone plus childhood low-dose estrogen in Turner's syndrome. N Engl J Med 2011; 364:1230–42.

This article explains the editorial's content in plain language while preserving all numerical data, study details, and conclusions. It does not replace individualized medical advice from a qualified health care provider.