Tall stature : morbidity, mortality and treatment outcomes

Tall stature is usually constitutional. In some cases excessive growth is caused by early puberty and in others by growth disorders such as Marfan syndrome or pituitary gigantism. Some individuals experience a substantial negative psychosocial impact from being tall which can cause them and their families to seek medical attention. Whether or not to reduce adult height is an ethical dilemma where the psychological benefits must be weighed carefully against possible health complications. For over half a century, adolescent boys and girls have been treated with high-dose sex steroids in an attempt to reduce their adult heights by inducing early growth plate closure. In the late 1990s, another treatment option was introduced, so called epiphysiodesis, where growth plate cartilage in the lower extremities was surgically destroyed to stop further growth in tall adolescents. The overall aim of this thesis was to evaluate health consequences of the two principally different methods to reduce further growth in extremely tall adolescents and to study how height affects health.

In paper I we performed a cohort study of the cancer risk in 369 women who were assessed for tall stature during their adolescence at Swedish university hospitals between 1973 and 1993 and were followed for a median period of 27 years. Approximately half of them were treated with a median daily dose of 500 μg ethinyl oestradiol and the rest were untreated. The odds ratio (OR) for developing melanoma in treated compared to untreated was 6.1 (1.04-∞). The ORs for overall tumours and breast cancer were increased, but the risk estimates were imprecise.

In paper II we studied the efficacy and safety of percutaneous epiphysiodesis, in 21 operated boys and girls who were followed until reaching adult height. When compared to prediction, adult height was reduced by 4.1+/-0.7 cm in treated girls (P<0.001) and 6.4 +/- 0.7 cm in treated boys (P<0.001), corresponding to a third of predicted remaining growth in both genders. No serious side effects were reported during follow-up.

In paper III, the extensive Swedish population registers enabled us to study how height was associated with cancer and mortality in a very large cohort of five and a half million Swedish men and women born 1938-1991. Hazard ratio (HR) for any cancer per 10 cm increase in height was 1.19 (1.18, 1.20) in women and 1.11 (1.10, 1.12) in men. All 15 specific cancer sites studied were positively associated with height, melanoma most strongly so with HR 1.39 (1.35, 1.43) in women and 1.32 (1.28, 1.36) in men. Cancer mortality was increased with height in both genders whereas a number of other specific death causes, including cardiovascular disease, were decreased with height. Overall mortality was not notably affected by height in women, HR 0.98 (0.97 - 0.99), but decreased in taller men, HR 0.91 (0.90 - 0.92).

In summary, this thesis contributes to the understanding of how an individual’s health is affected by height per se as well as by different height reduction therapies. This knowledge can facilitate better management of individuals who seek medical attention for tall stature.

List of scientific papers

I. Benyi E, Kieler H, Linder M, Ritzén M, Carlstedt-Duke J, Tuvemo T, Westphal O, Sävendahl L. Risks of malignant and non-malignant tumors in tall women treated with high-dose estrogen during adolescence. Horm Res Paediatr. 2014;82:89-96.
https://doi.org/10.1159/000360137

II. Benyi E, Berner M, Bjernekull I, Boman A, Chrysis D, Nilsson O, Waehre A, Wehtje A, Sävendahl L. Efficacy and Safety of Percutaneous Epiphysiodesis Operation around the Knee to Reduce Adult Height in Extremely Tall Adolescent Girls and Boys. International Journal of Pediatric Endocrinology. 2010;2010:740629.
https://doi.org/10.1155/2010/740629

III. Benyi E, Linder M, Adami J, Kieler H, Palme M, Sävendahl L. Adult height associated with cancer risk and mortality in 5.5 million Swedish women and men. [Manuscript]