Growth Hormone Combined With Stanozolol in Turner Syndrome
Objective Turner syndrome (TS), which is characterized by short stature and gonadal dysfunction, is managed by pharmacotherapy. This study aimed to investigate the therapeutic effects of recombinant human growth hormone (rhGH) combined with low-dose stanozolol on the growth and final adult height (FAH) of girls with Turner syndrome (TS).
Design Prospective study.
Patients A total of 44 girls with TS were treated with rhGH (47·6–52·4 μg/kg/day) and low-dose stanozolol (20–35 μg/kg/day), starting at a mean age of 12·65 ± 1·99 year. The control group consisted of 22 girls with TS, who did not receive treatment.
Measurements Subjects' growth velocity (GV) was investigated. Height standard deviation score (HtSDS) was calculated relative to healthy Chinese girls (HtSDSNor) as well as untreated Chinese girls with TS (HtSDSTS). Post-treatment follow-up was performed until the subjects achieved FAH or near FAH.
Results FAH was significantly higher in subjects receiving treatment compared to the untreated controls (151·42 vs 137·75 cm, P < 0·001). GV was significantly higher in the first to fourth years of treatment compared to baseline values (P < 0·001); it was significantly lower in the second to fourth years of treatment compared to the first year (P < 0·001).
Conclusions In girls with TS, 9–12 years of age, rhGH combined with low-dose stanozolol may effectively increase growth. At least a 2-year course of this treatment may effectively improve FAH with proper delay of oestrogen-induced development.
Turner syndrome (TS), also known as congenital ovarian dysgenesis syndrome, affects 1 in 2500 female neonates and is associated with loss of all or part of the X chromosome, including deletion of the short or long arms. TS is clinically characterized as the combination of short stature, gonadal dysgenesis, typical visible dysmorphic stigmata, and urinary, cardiovascular and skeletal abnormalities associated with a missing or structurally abnormal second sexual chromosome. Thus, a majority of girls with TS are diagnosed in peripuberty.
Females with TS are haploinsufficient for genes that are normally expressed by both X chromosomes. Depending on parental origin, specific phenotypes may influence short stature and other clinical features of TS, which may be more severe in females with the 45,X karyotype. However, a recent study showed that the parental origin of the retained X chromosome may influence lipid metabolism with only a minimal effect on growth. No parental origin effect on phenotypic features, associated anomalies or growth response to rhGH was found in 45,X individuals with TS.
TS is managed through pharmacotherapy, which aims to achieve normal height and sexual maturity. In 1985, recombinant human growth hormone (rhGH) was approved by the US Food & Drug Administration (FDA) for treating growth hormone (GH) deficiency. Shortly thereafter, it was approved for conditions without GH deficiency, including TS. Although the initial studies indicated that girls with TS could gain 7·2 cm in height over 5 years of treatment with GH, more recent studies have modified the gain to 5 cm after 7 years of treatment. Nevertheless, it has become clear that early diagnosis and treatment of TS may help patients to achieve normal final adult height (FAH), especially when early rhGH therapy is administered at a sufficient dosage. Thus, GH therapy should be considered as soon as decreased linear GV becomes obvious. Alternatively, some investigators have attempted to increase the rhGH dose in order to elevate the therapeutic efficacy. However, this has been associated with increased insulin growth factor-1 (IGF-1) and insulin levels, which may increase the risk of side effects; it also significantly elevates the cost of therapy.
In patients with TS, GH therapy is followed by oestrogen therapy to induce puberty. Addition of low-dose anabolic steroids that are not converted to oestrogens, including 17α-alkylated androgen (e.g. oxandrolone and stanozolol), can also accelerate bone growth, but not maturation, thereby increasing the therapeutic effects of rhGH. For example, low-dose oxandrolone significantly increased GV and improved FAH in patients with TS compared to rhGH alone. In a small sample of patients with TS, we have also shown that low-dose stanozolol improved the growth velocity. Fang et al. also showed that rhGH and stanozolol increased the growth velocity and predicted adult height in girls with TS. Similarly, cotreatment of stanozolol with a gonadotropin-releasing hormone analogue improved height in two patients who entered puberty with short stature. However, to our knowledge, no further study has been conducted to investigate the therapeutic efficacy of rhGH in combination with low-dose stanozolol in girls with TS. Thus, the objective of the present ongoing prospective study was to report our experience in the treatment of TS with rhGH and low-dose stanozolol.
Abstract and Introduction
Abstract
Objective Turner syndrome (TS), which is characterized by short stature and gonadal dysfunction, is managed by pharmacotherapy. This study aimed to investigate the therapeutic effects of recombinant human growth hormone (rhGH) combined with low-dose stanozolol on the growth and final adult height (FAH) of girls with Turner syndrome (TS).
Design Prospective study.
Patients A total of 44 girls with TS were treated with rhGH (47·6–52·4 μg/kg/day) and low-dose stanozolol (20–35 μg/kg/day), starting at a mean age of 12·65 ± 1·99 year. The control group consisted of 22 girls with TS, who did not receive treatment.
Measurements Subjects' growth velocity (GV) was investigated. Height standard deviation score (HtSDS) was calculated relative to healthy Chinese girls (HtSDSNor) as well as untreated Chinese girls with TS (HtSDSTS). Post-treatment follow-up was performed until the subjects achieved FAH or near FAH.
Results FAH was significantly higher in subjects receiving treatment compared to the untreated controls (151·42 vs 137·75 cm, P < 0·001). GV was significantly higher in the first to fourth years of treatment compared to baseline values (P < 0·001); it was significantly lower in the second to fourth years of treatment compared to the first year (P < 0·001).
Conclusions In girls with TS, 9–12 years of age, rhGH combined with low-dose stanozolol may effectively increase growth. At least a 2-year course of this treatment may effectively improve FAH with proper delay of oestrogen-induced development.
Introduction
Turner syndrome (TS), also known as congenital ovarian dysgenesis syndrome, affects 1 in 2500 female neonates and is associated with loss of all or part of the X chromosome, including deletion of the short or long arms. TS is clinically characterized as the combination of short stature, gonadal dysgenesis, typical visible dysmorphic stigmata, and urinary, cardiovascular and skeletal abnormalities associated with a missing or structurally abnormal second sexual chromosome. Thus, a majority of girls with TS are diagnosed in peripuberty.
Females with TS are haploinsufficient for genes that are normally expressed by both X chromosomes. Depending on parental origin, specific phenotypes may influence short stature and other clinical features of TS, which may be more severe in females with the 45,X karyotype. However, a recent study showed that the parental origin of the retained X chromosome may influence lipid metabolism with only a minimal effect on growth. No parental origin effect on phenotypic features, associated anomalies or growth response to rhGH was found in 45,X individuals with TS.
TS is managed through pharmacotherapy, which aims to achieve normal height and sexual maturity. In 1985, recombinant human growth hormone (rhGH) was approved by the US Food & Drug Administration (FDA) for treating growth hormone (GH) deficiency. Shortly thereafter, it was approved for conditions without GH deficiency, including TS. Although the initial studies indicated that girls with TS could gain 7·2 cm in height over 5 years of treatment with GH, more recent studies have modified the gain to 5 cm after 7 years of treatment. Nevertheless, it has become clear that early diagnosis and treatment of TS may help patients to achieve normal final adult height (FAH), especially when early rhGH therapy is administered at a sufficient dosage. Thus, GH therapy should be considered as soon as decreased linear GV becomes obvious. Alternatively, some investigators have attempted to increase the rhGH dose in order to elevate the therapeutic efficacy. However, this has been associated with increased insulin growth factor-1 (IGF-1) and insulin levels, which may increase the risk of side effects; it also significantly elevates the cost of therapy.
In patients with TS, GH therapy is followed by oestrogen therapy to induce puberty. Addition of low-dose anabolic steroids that are not converted to oestrogens, including 17α-alkylated androgen (e.g. oxandrolone and stanozolol), can also accelerate bone growth, but not maturation, thereby increasing the therapeutic effects of rhGH. For example, low-dose oxandrolone significantly increased GV and improved FAH in patients with TS compared to rhGH alone. In a small sample of patients with TS, we have also shown that low-dose stanozolol improved the growth velocity. Fang et al. also showed that rhGH and stanozolol increased the growth velocity and predicted adult height in girls with TS. Similarly, cotreatment of stanozolol with a gonadotropin-releasing hormone analogue improved height in two patients who entered puberty with short stature. However, to our knowledge, no further study has been conducted to investigate the therapeutic efficacy of rhGH in combination with low-dose stanozolol in girls with TS. Thus, the objective of the present ongoing prospective study was to report our experience in the treatment of TS with rhGH and low-dose stanozolol.
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