Various factors, including genetics, nutritional status, illnesses, and hormone levels may influence height development.1 Height improvement in short-statured girls poses a challenging problem due to estrogen derived from the adrenal gland and other peripheral tissues. Estrogen induces epiphyseal fusion, which limits the time for height growth and results in unsatisfactory adult height (AH).2 The use of gonadotropin-releasing hormone analog (GnRHa) could suppress ovarian estrogen synthesis effectively, delay bone age (BA) progression, and allow for more linear growth time. In girls with a BA of <12.5 years, the treatment approach of GnRHa and recombinant human growth hormone (rhGH) has shown promising results.3 However, in girls with a BA of >12.5 years (epiphyseal closure typically occurs approximately 12 to 13 years in Asian females), the growth plates are approaching closure. Estrogen from the adrenal gland and adipocytes may continue to promote this process. Consequently, the GnRHa and rhGH regimen has limited benefits for height improvement in such patients.

Aromatase is an enzyme present on cytochrome P450 (CYP19A1) and catalyzes the conversion of androgens (eg, androstenedione and testosterone) into estrogens.4 Letrozole is a third-generation aromatase inhibitor (AI) that can inhibit over 99.1% of estrogen production.5 It is used in the treatment of polycystic ovary syndrome for ovulation induction and in patients with peripheral precocious puberty caused by McCune-Albright syndrome. AIs block the conversion of androgens to estrogens, delay BA progression, allow for normal masculinization, and stimulate longitudinal bone growth through androgen receptor action on the growth plate,6 thereby improving the height of patients. Studies conducted on boys with constitutional growth delay,7 idiopathic short stature,8 and growth hormone (GH) deficiency9 have shown that the use of AI alone or in combination with rhGH may increase the final AH by delaying epiphyseal fusion. However, there have been rare data on letrozole for height improvement in girls with short stature. The use of letrozole alone in girls may lead to an increase in in the gonadotropin levels. Therefore, GnRHa should be used simultaneously to suppress gonadotropins. This study reports on 29 female patients from our hospital who received combined treatment with rhGH, GnRHa, and letrozole for a duration of >6 months.