Growth hormone therapy of Turner's syndrome: beneficial effect on adult height. Three-year results of treatment with growth hormone, alone or associated with oxandrolone, in girls with Turner syndrome. The Kabi Collaborative Study Group. Growth hormone therapy in Turner's syndrome: an update on final height. Genentech National Cooperative Study Group. Six-year results of a randomized, prospective trial of human growth hormone and oxandrolone in Turner syndrome. Final height outcome in girls with Turner syndrome treated with a combination of low dose oestrogen and oxandrolone Methionyl human growth hormone and oxandrolone in Turner syndrome: preliminary results of a prospective randomized trial. Favorable Final Height Outcome in Girls with Ullrich-Turner Syndrome Treated with Low-Dose Growth Hormone Together with Oxandrolone Despite Starting Treatment After 10 Years of Age Growth promotion and Turner-specific bone age after therapy with growth hormone and in combination with oxandrolone: when should therapy be started in Turner syndrome? Long-term effects of previous oxandrolone treatment in adult women with Turner syndrome. Prospective Study Confirms Oxandrolone-Associated Improvement in Height in Growth Hormone-Treated Adolescent Girls with Turner Syndrome Non-conventional growth hormone therapy in Turner syndrome: the United States experience. Efficacy and safety of oxandrolone in growth hormone-treated girls with turner syndrome. Effect of oxandrolone and timing of pubertal induction on final height in Turner’s syndrome: randomised, double blind, placebo controlled trial Three-year results of a randomized prospective trial of methionyl human growth hormone and oxandrolone in Turner syndrome. Recombinant human growth hormone and oxandrolone in treatment of short stature in girls with Turner syndrome. The effect of the weak androgen oxandrolone on psychological and behavioral characteristics in growth hormone-treated girls with Turner syndrome Demography, auxology and response to recombinant human growth hormone treatment in girls with Turner's syndrome in the Kabi Pharmacia International Growth Study
OBJECTIVE To carry out a multicenter , prospect i ve , r and omized trial of human growth hormone ( GH ) , alone or in combination with ox and rolone ( OX ) , in patients with Turner 's syndrome ( TS ) . METHODS In an initial phase lasting 12 to 24 months , 70 girls with TS , verified by karyotype , were r and omly assigned to one of four groups : ( 1 ) observation , ( 2 ) OX , ( 3 ) GH , or ( 4 ) GH plus OX . After completion of the first phase , group 3 subjects continued to receive GH only . All other subjects were treated with GH plus OX . Subjects were followed up until attainment of adult height and /or cessation of treatment . Data from this trial were compared with growth characteristics of 25 American historical subjects with TS ( matched for age , height , parental target height , and karyotype ) who never received either GH or and rogens .  RESULTS Of the 70 subjects enrolled , 60 completed the clinical trial . The 17 subjects receiving GH alone all completed the trial and reached a height of 150.4+/-5.5 cm ( mean + /- SD ) , 8.4+/-4.5 cm taller than their mean projected adult height at enrollment ( 95 % confidence interval [ CI ] : 6.3 to 10.6 cm ) . The 43 subjects receiving GH plus OX attained a mean height of 152.1+/-5.9 cm , 10.3+/-4.7 cm taller than their mean projected adult height ( 95 % CI : 8.9 to 11.7 cm ) . The historical control subjects had a mean adult height of 144.2+/-6.0 cm , precisely matching their original projected adult height of 144.2+/-6.1 cm . CONCLUSIONS GH , either alone or in combination with OX , is capable of stimulating short-term growth and augmenting adult height in girls with TS . With early diagnosis and initiation of treatment , an adult height of more than 150 cm is a reasonable goal for most girls with TS 22 girls with Turner syndrome aged 10.8 + /- 2.4 years with bone age 8.58 + /- 1.32 years , r and omized in two groups , were treated for 3 years with either growth hormone ( GH ) , 0.1 U/kg daily ( group A ) , or GH , 0.1 U/kg , plus ox and rolone , 0.06 mg/kg ( group B ) . This result ed in a sharp increase in growth rate for the first year of treatment , followed in the second and third years by a growth rate near to the normal mean for age . The growth velocity was better in group B , the difference being significant during the first year only . After 3 years , the predicted adult height had increased by 2.1 cm as a mean in group A and by 4.5 cm in group B , with important individual variations , result ing in a gain of at least 3 cm in 3/10 patients of group A and 9/12 of group B. No metabolic or other side effects occurred . These 3-year data confirm that GH improves the predictable height in Turner girls . They suggest that it may be useful for at least 3 years and that adding a small dose of ox and rolone for 2 years in girls aged more than 8 years could be of good practice . However , earlier and more protracted treatment with GH has to be studied with the hope to better improve the predictable adult height The Genentech National Cooperative Study of growth hormone ( GH ) therapy in Turner 's syndrome was initiated in 1983 ; 70 girls with Turner 's syndrome were r and omly assigned to observation or to treatment with GH alone , ox and rolone alone , or a combination of GH plus ox and rolone for a period of 12 - 24 months . After completion of this phase , patients receiving GH alone were continued on GH , while all other patients received the combination of GH plus ox and rolone . Data are currently available on the 62 girls who were treated for a minimum of 3 - 6 years . When compared with the height velocities anticipated for girls of comparable ages with untreated Turner 's syndrome , both GH alone and a combination of GH plus ox and rolone result ed in an increase in height velocity , which was most prominent during the first 2 years of treatment and was sustained for at least 6 years . Although GH therapy is continuing at present in half of the patients , 14 of 17 girls ( 82 % ) receiving GH alone and 42 of 45 girls ( 93 % ) receiving combination therapy have exceeded their projected adult heights . For the 30 girls who have stopped therapy , the current mean height is 151.9 cm , compared with their original mean projected adult height of 143.8 cm . These results demonstrate that GH therapy can result in short-term ( 3 - 6 years ) acceleration of growth , as well as in improved adult height Seventy girls with Turner syndrome , verified by karyotype , were r and omly assigned to observation or treatment with human growth hormone ( hGH ) , ox and rolone , or a combination of hGH plus ox and rolone for a period of 12 to 24 months , to assess the effect of treatment on growth velocity and adult height . Subsequently , all subjects received either hGH alone or hGH plus ox and rolone . Data are presented for 62 subjects treated for a period of 3 to 6 years . When compared with the anticipated growth rate in untreated patients , the growth rate after treatment with hGH , both alone and in combination with ox and rolone , showed a sustained increase for at least 6 years . Treatment is continuing in over half of the subjects ; at present , 14 ( 82 % ) of 17 girls receiving hGH alone and 41 ( 91 % ) of 45 girls receiving combination therapy exceeded their expected adult heights .  Thirty girls have completed treatment ; mean height for these 30 patients is 151.9 cm , compared with their mean original projected adult height of 143.8 cm . We conclude that therapy with hGH , alone and in combination with ox and rolone , can result in a sustained increase in growth rate and a significant increase in adult height for most prepubertal girls with Turner syndrome Abstract  Final stature in girls with Turner syndrome treated with combination of low dose oestrogen and ox and rolone .  Nineteen prepubertal girls with Turner syndrome ( mean age 10.9 years , range , 8.9–14.2 years ) were r and omly assigned to receive either ox and rolone ( 0.05 mg/kg/day ) or ethinyloestradiol ( 40 ng/kg/day ) for 1 year . Subsequently the alternate therapy was added and the combination given until attainment of final height . Ethinyloestradiol was gradually increased at the age of 12.5 years in order to induce secondary sexual characteristics . The duration of treatment was a mean of 5.2 years ( range , 3–7 years ) when the 1st year of monotherapy was included . Therapy produced a sustained acceleration in growth rate for a duration of 4 years and eventually has result ed in an increment of mean adult height of 3 cm relative to pre-treatment projected height with mean values of 146.5 cm versus 143.5 cm respectively . The moderate side-effects observed did not cause any of the girls to discontinue treatment . Nevertheless , amelioration of adult height appears to be modest , notably in comparison to published data of growth hormone treatment and 4 girls had a decrease in final height prediction . Conclusion Combination of low dose of ox and rolone and oestrogen may have a moderate but positive impact on final height  in girls with Turner syndrome . However , some girls do worse than predicted in term of final height using this regimen . Oestrogen therapy started at low dose around the age of 10 years and increased gradually at approximately 12.5 years to induce secondary sexual characteristics does not have a deleterious effect on adult height in Turner syndrome . In summary , low dose ox and rolone-oestrogen treatment was found to accelerate the tempo of growth in girls with Turner syndrome , but did not appear to have a consistent effect on final height Seventy girls with Turner syndrome , 4 to 12 years of age , were r and omly assigned to receive either no treatment ( control ) or methionyl human growth hormone ( 0.125 mg/kg three times per week ) , ox and rolone ( 0.125 mg/kg/day ) , or combination hGH plus ox and rolone therapy .  Baseline growth rates averaged 4.3 cm/yr , and all were within 2 SD of mean growth velocity for age in girls with Turner syndrome . Sixty-seven girls remained in the study for a minimum of 1 year . Growth rates and growth velocity ( in st and ard deviations for age in girls with Turner syndrome ) were control 3.8 cm/yr ( -0.1 SD ) , hGH 6.6 cm/yr ( + 2.3 SD ) , ox and rolone 7.9 cm/yr ( + 3.7 SD ) , and combination therapy 9.8 cm/yr ( + 5.4 SD ) . Mean bone ages advanced 1.0 years ( hGH ) , 1.3 years ( ox and rolone ) , and 1.6 years ( combination ) . However , median increments in height age/bone age ( delta HA/delta BA ) ratios ranged from 1.0 to 1.1 for treatment groups , compared with 0.8 for the controls . Predicted adult height by the method of Bayley-Pinneau increased 2.5 cm for hGH or ox and rolone alone , and 3.2 cm for combination treatment . These data indicate that both hGH and ox and rolone can significantly stimulate short-term skeletal growth in patients with Turner syndrome , and potentially increase final adult height The objective of this study was to find out whether moderate doses of growth hormone ( GH ) in combination with ox and rolone ( Ox ) and late initiation of puberty could improve adult height even in relatively old patients with Ullrich-Turner syndrome ( UTS ) . Ninety-one patients with UTS were r and omly assigned to receive either GH alone ( Saizen , Ares-Serono , Geneva ) 18 IU/m2/week ( 0.2 mg/kg/week ) by daily s.c . injections ( group GH ) or a combination of GH and Ox 0.1 mg/kg/day p.o . ( group GH + Ox ) . Prior to treatment mean age was 10.2 years ( GH ) and 10.5 years ( GH + Ox ) , mean projected adult height ( PAH ) was 146.4 cm ( GH ) and 146.7 cm ( GH + Ox ) . During year 2 the GH dose was increased in the GH group to 24 and later to 28 IU/m2/week ( 0.27 mg and later 0.31 mg/kg/week ) . In group GH + Ox , the Ox dose was reduced to 0.05 mg/kg/day after the first 12 months of therapy , and during the last treatment years the GH dose was raised to 24 - 28 IU/m2/week ( 0.27 - 0.31 mg/kg/week ) due to declining growth promotion . Some of the patients of group GH were later given Ox in addition to GH because of waning growth velocity , whereas some of the patients of group GH + Ox were taken off Ox due to virilizing side-effects of the high Ox dose , thus making up a third group of patients : group GH + transient Ox . Puberty was induced at a mean age of 14.9 years . In group GH + Ox , cumulative growth during 5 years of therapy was twice the growth anticipated from st and ards of untreated patients with UTS . Forty-seven patients are now near or at final height : in group GH ( n = 7 ) , mean final height was 151.7 cm ( PAH 148.1 cm , gain 3.6 cm ) ; in group GH + Ox ( n = 15 ) , 155.1 cm ( PAH 147.2 cm , gain 7.9 cm ) ; and in group GH + transient Ox ( n = 25 ) , 152.8 cm ( PAH 146.4 cm , gain 6.4 cm ) . These results should be regarded as an underestimate of true final height since some the patients are still growing . Moderate doses of GH plus Ox and late induction of puberty definitely improved final height even in patients with UTS treated relatively late The aims of this comparative multicenter study of 67 girls with Turner syndrome ( TS ) on three different therapeutical regimens were , first , to evaluate the effect of either recombinant human growth hormone ( GH ) alone or in combination with the anabolic steroid ox and rolone ( Oxa ) on height velocity and on Turner-specific bone age ( BA'TS ) and , second , to estimate the gain in final height taking the age at the onset of treatment into account . The mean advancement of BA'TS in 2 years of treatment was 2.5 years/2 years in group 1 ( low dose GH : 16 IU/m2/week ) , 2.8 years/2 years in group 2 ( high dose GH : 28 IU/m2/week ) and 3.3 years/2 years in group 3 ( GH : 24 IU/m2/week + Oxa : 0.06 mg/kg/day ) instead of the expected 2 years/2 years advancement in untreated girls with TS . On all treatment regimens the advancement of BA'TS was more pronounced in the younger girls . In many girls with a BA'TS below 9 years at the onset of treatment the increase in height did not outweigh the advancement in BA'TS , suggesting that starting growth-promoting treatment before 9 years would not be the best way to improve final height . In our opinion , the optimal age for starting growth-promoting therapy is at 9 years . A start at a younger age might have no advantage in regard of an ultimate gain in final height . On the other h and , therapy should not be delayed much after the age of 9 years giving the girls with TS the possibility to catch up substantially before estrogen treatment is initiated OBJECTIVE Short stature is a prominent feature of Turner syndrome ( TS ) , which is partially overcome by GH treatment . We have previously reported the results of a trial on the effect of ox and rolone ( Ox ) in girls with TS . Ox in a dose of 0.03 mg/kg per day ( Ox 0.03 ) significantly increased adult height gain , whereas Ox mg/kg per day ( 0.06 ) did not , at the cost of deceleration of breast development and mild virilization . The aim of this follow-up study in adult participants of the pediatric trial was to investigate the long-term effects of previous Ox treatment . DESIGN AND METHODS During the previous r and omized controlled trial , 133 girls were treated with GH combined with placebo ( Pl ) , Ox 0.03 , or Ox 0.06  from 8 years of age and estrogen from 12 years . Sixty-eight women ( Pl , n=23 ; Ox 0.03 , n=27 ; and Ox 0.06 , n=18 ) participated in the double-blind follow-up study ( mean age , 24.0 years ; mean time since stopping GH , 8.7 years ; and mean time of Ox/Pl use , 4.9 years ) . We assessed height , body proportions , breast size , virilization , and body composition . RESULTS Height gain ( final minus predicted adult height ) was maintained at follow-up ( Ox 0.03 10.2±4.9 cm , Ox 0.06 9.7±4.4 cm vs Pl 8.0±4.6 cm ) . Breast size , Tanner breast stage , and body composition were not different between groups . Ox-treated women reported more subjective virilization and had a lower voice frequency . CONCLUSION Ox 0.03 mg/kg per day has a beneficial effect on  adult height gain in TS patients . Despite previously reported deceleration of breast development during Ox 0.03 treatment , adult breast size is not affected . Mild virilization persists in only a small minority of patients . The long-term evaluation indicates that Ox 0.03 treatment is effective and safe Background / Aims : Untreated girls with Turner syndrome ( TS ) have growth failure , and adult height is , on average , 20 cm less than predicted height . Treatment with growth hormone ( GH ) is now st and ard of care . The objective of this study was to investigate the benefit of adding ox and rolone ( Ox ) to GH in a long-term , r and omized , placebo (Pl)-controlled prospect i ve trial to near adult height in TS . Methods : Prospect i ve , r and omized , Pl-controlled study : 76 girls with TS ( ages 10–14.9 years ) were r and omized to receive Ox ( 0.06 mg/kg/day ) or Pl in combination with GH ( 0.35 mg/kg/week , daily ) over 2 years . Auxologic data , breast and pubic hair Tanner stages , and hormone and lipid levels were measured . Subjects who chose to continue were followed in a 2-year double-blind extension , also received estrogen therapy ( years 3 , 4 ) , and had dual-energy X-ray absorptiometry evaluation of bone density ( years 3 , 4 ) . Results : At year 4 , the change in absolute height and height SDS was greater in the GH/Ox versus GH/Pl group [ 26.2 ± 6.7 vs. 22.2 ± 5.1 cm , analysis of covariance ( ANCOVA ) p < 0.001 ; 1.8 ± 0.9 vs. 1.2 ± 0.7 st and ard deviation scores , ANCOVA p < 0.001 ] . Bone mineral density ( BMD ) of the wrist ( 0.51 ± 0.17 vs. 0.54 ± 0.05 g/cm2 ) and spine ( 0.91 ± 0.34 vs. 0.96 ± 0.13 g/cm2 ) in the GH/Ox versus GH/Pl groups was similar after 4 years . Breast development was slower in the GH/Ox versus GH/Pl group [ year 4 : Tanner stage 2.9 ±1.3 ( Ox ) vs. 4.1 ± 1.3 ( Pl ) , p = 0.003 ] , and menarche was approximately 1 year later . Conclusions : The addition of Ox to GH at mean age 12.0 ± 1.7 year augmented height gain after 4 years of treatment , slowed breast development and did not affect BMD in girls with TS . Whether initiation of Ox prior to initiation of pubertal development would optimize height gain without impeding breast development will require further study Beginning in 1983 , 71 girls with Turner syndrome were enrolled in a prospect i ve , r and omized study of human growth hormone ( hGH ) , alone and in combination with ox and rolone ; 4 - 5 patient-year data are currently available on 66 subjects . While the annual growth rate of the untreated control group ( expressed as a Z score for untreated Turner girls ) was -0.1 SD , the annual Turner growth rate Z scores for girls receiving hGH alone were + 3.1 , + 2.0 , + 1.5 and + 2.9 SD for years 1 - 4 , respectively ( hGH was given daily in year 4 ) . mean annual Turner growth rate Z scores for subjects on combination therapy with ox and rolone were + 6.6 , + 4.3 , + 3.0 and + 2.7 SD for years 1 - 4 , respectively . The mean height for the 20 subjects greater than or equal to 16 years of age is 150 cm CONTEXT AND OBJECTIVE GH therapy increases growth and adult height in Turner syndrome ( TS ) . The benefit to risk ratio of adding the weak and rogen ox and rolone ( Ox ) to GH is unclear . DESIGN AND PARTICIPANTS A r and omized , placebo-controlled , double-blind , dose-response study was performed in 10 centers in The Netherl and s. One hundred thirty-three patients with TS were included in age group 1 ( 2 - 7.99 yr ) , 2 ( 8 - 11.99 yr ) , or 3 ( 12 - 15.99 yr ) . Patients were treated with GH ( 1.33 mg/m(2 ) . d ) from baseline , combined with placebo ( Pl ) or Ox in low ( 0.03 mg/kg . d ) or conventional ( 0.06 mg/kg . d ) dose from the age of 8 yr and estrogens from the age of 12 yr . Adult height gain ( adult height minus predicted adult height ) and safety parameters were systematic ally assessed . RESULTS Compared with GH+Pl , GH+Ox 0.03 increased adult height gain in the intention-to-treat analysis ( mean + /- sd , 9.5 + /- 4.7 vs. 7.2 + /- 4.0 cm , P = 0.02 ) and per- protocol analysis ( 9.8 + /- 4.9 vs. 6.8 + /- 4.4 cm , P = 0.02 ) . Partly due to accelerated bone maturation ( P < 0.001 ) , adult height gain on GH+Ox 0.06 was not significantly different from that on GH+Pl ( 8.3 + /- 4.7 vs. 7.2 + /- 4.0 cm , P = 0.3 ) . Breast development was slower on GH+Ox ( GH+Ox 0.03 , P = 0.02 ; GH+Ox 0.06 , P = 0.05 ) , and more girls reported virilization on GH+Ox 0.06 than on GH+Pl ( P < 0.001 ) . CONCLUSIONS In GH-treated girls with TS , we discourage the use of the conventional Ox dosage ( 0.06 mg/kg . d ) because of its low benefit to risk ratio . The addition of Ox 0.03 mg/kg . d modestly increases adult height gain and has a fairly good safety profile , except for some deceleration of breast development Objective To examine the effect of ox and rolone and the timing of pubertal induction on final height in girls with Turner ’s syndrome receiving a st and ard dose of growth hormone . Design R and omised , double blind , placebo controlled trial . Setting 36 paediatric endocrinology departments in UK hospitals . Participants Girls with Turner ’s syndrome aged 7 - 13 years at recruitment , receiving recombinant growth hormone therapy ( 10 mg/m2/week ) . Interventions Participants were r and omised to ox and rolone ( 0.05 mg/kg/day , maximum 2.5 mg/day ) or placebo from 9 years of age . Those with evidence of ovarian failure at 12 years were further r and omised to oral ethinylestradiol ( year 1 , 2 µg daily ; year 2 , 4 μg daily ; year 3 , 4 months each of 6 , 8 , and 10 μg daily ) or placebo ;  participants who received placebo  and those recruited after the age of 12.25 years  started ethinylestradiol at age 14 . Main outcome measure Final height . Results 106 participants were recruited , of whom 14 withdrew and 82/92 reached final height . Both ox and rolone and late pubertal induction increased final height : by 4.6 ( 95 % confidence interval 1.9 to 7.2 ) cm ( P=0.001 , n=82 ) for ox and rolone and 3.8 ( 0.0 to 7.5 ) cm ( P=0.05 , n=48 ) for late pubertal induction with ethinylestradiol . In the 48 children who were r and omised twice , the effects on final height ( compared with placebo and early induction of puberty ) of ox and rolone alone , late induction alone , and ox and rolone plus late induction were similar , averaging 7.1 ( 3.4 to 10.8 ) cm ( P<0.001 ) . No cases of virilisation were reported . Conclusion Ox and rolone had a positive effect on final height in girls with Turner ’s syndrome treated with growth hormone , as did late pubertal induction with ethinylestradiol at age 14 years . However , these effects were not additive , so using both had no advantage . Ox and rolone could , therefore , be offered as an alternative to late pubertal induction for increasing final height in Turner ’s syndrome . Trial registration Current Controlled Trials IS RCT N50343149 Seventy girls with Turner syndrome , 4 to 12 years of age , participated in a prospect i ve , r and omized study to determine the effects on growth of methionyl human growth hormone ( met-hGH ) or ox and rolone . Subjects were r and omly assigned to receive either no treatment ( control ) or met-hGH ( 0.125 mg/kg three times per week ) , ox and rolone ( 0.125 mg/kg/day ) , or combination met-hGH plus ox and rolone . At the end of an initial period of 12 to 20 months , patients in the original control and ox and rolone groups were given combination met-hGH plus ox and rolone . At that time the dosage of ox and rolone was lowered to 0.0625 mg/kg/day . Sixty-five subjects have now completed the first 3 years of the study . Compared with the control growth rate for year 1 ( 3.8 cm/yr ) , significant increases in growth rate were seen in all 3 years of combination therapy ( 9.8 , 7.4 , and 6.1 cm/yr , respectively ) and in the first 2 years of treatment with met-hGH alone ( 6.6 , 5.4 , and 4.6 cm/yr ) . When growth velocity was expressed as st and ard deviation for age in girls with Turner syndrome , significant increases relative to the control group for year 1 ( -0.1 SD ) were seen in all three years of both combination therapy and met-hGH alone ( combination , + 6.6 , + 4.3 , + 3.0 SD ; met-hGH , + 3.1 , + 2.0 , + 1.4 SD ) . After 3 years of treatment , predicted adult height by the method of Bayley-Pinneau increased 4.5 cm in the met-hGH group and 8.2 cm in the combination group 91 girls with Turner syndrome ( TS ) with a mean chronological age ( CA ) and bone age ( BA ) of 10.3 + /- 2.3 and 8.9 + /- 1.9 years , respectively , were r and omly assigned to subcutaneous treatment with recombinant human growth hormone ( rhGH ) alone ( n = 47 ) , 2.6 IU/m2 body surface area daily or combination treatment ( n = 44 ) with the same dose of rhGH and ox and rolone 0.1 mg/kg body weight orally , for the first 12 months of this study . During the 1st year of therapy , there was a striking increase in height velocity ( HV ) in both groups , from 4.0 + /- 0.8 to 6.3 + /- 1.3 cm/year [ HV st and ard ( st and ards of untreated Turner patients ) deviation score ( SDS ) for CA from 0.0 + /- 0.7 to 2.9 + /- 1.3 ] in the rhGH group and from 4.2 + /- 1.2 to 8.5 + 2- 1.7 cm/year ( HV SDS-CA from + 0.3 + /- 1.0 to 5.6 + /- 1.6 ) in the combination group . The difference between the groups was statistically significant ( p < 0.01 ) . During the 2nd year of treatment , the rhGH dose was increased to 3.4 IU/m2 daily for the rhGH-alone group , whereas in the combination treatment group the ox and rolone dose was reduced to 0.05 mg/kg daily . HV was maintained at significantly higher levels than those prior to treatment , at 5.3 + /- 1.1 cm/year ( HV SDS-CA : + 2.1 + /- 1.3 ) and 6.2 + /- 1.5 cm/year ( HV SDS-CA : + 3.6 + /- 1.4 ) in the rhGH-alone and the combination group , respectively ( p < 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS The weak and rogen ox and rolone ( Ox ) increases height gain in growth-hormone ( GH ) treated girls with Turner syndrome ( TS ) , but may also give rise to virilizing side effects . To assess the effect of Ox , at a conventional and low dosage , on behavior , aggression , romantic and sexual interest , mood , and gender role in GH-treated girls with TS , a r and omized , placebo-controlled , double-blind study was conducted . 133 patients were treated with GH ( 1.33 mg/m(2)/d ) from baseline , combined with placebo ( Pl ) , Ox 0.03 mg/kg/d , or Ox 0.06 mg/kg/d from the age of eight , and with estrogens from the age of 12 . The child behavior checklist ( CBCL ) , Junior Dutch Personality Question naire ( DPQ-J ) , State-subscale of the Spielberger 's State-Trait Anger Scale , Romantic and Sexual Interest Question naire , Mood Question naire , and Gender Role Question naire were filled out before , during , and after discontinuing Ox/Pl . The changes during Ox/Pl therapy were not significantly different between the dosage groups . In untreated patients , the mean CBCL total ( P=0.002 ) and internalizing ( P=0.003 ) T scores , as well as the mean DPQ-J social inadequacy SD score ( SDS ) ( P=0.004 ) were higher than in reference girls , but decreased during GH+Ox/Pl therapy ( P<0.001 , P=0.05 , P<0.001 , respectively ) . Whereas the mean total ( P=0.01 ) and internalizing ( P<0.001 ) T score remained relatively high , the mean social inadequacy SDS became comparable with reference values . We conclude that in GH-treated girls with TS , Ox 0.03 mg/kg/d or 0.06 mg/kg/d does not cause evident psychological virilizing side effects . Problem behavior , frequently present in untreated girls with TS , decreases during therapy , but total and internalizing problem behavior remain increased Demographic and auxological data were analysed from 818 girls with Turner 's syndrome treated with recombinant human growth hormone ( GH ) and entered into the Kabi Pharmacia International Growth Study . Size at birth was low and correlated with the heights of both parents . The median age at start of GH  treatment was 11.4 years and the parents had a median height SDS of ‐2.9 . Height SDS at the start of treatment correlated with parental heights . Height velocities conformed to Turner‐specific st and ards . The weight‐for‐height index increased sharply above 9 years of age . The frequency of spontaneous appearance of Tanner breast stage 2 was high ( 34.1 % of girls > 10 years of age ) . Bone age ( Greulich and Pyle ) data were described by the equation : bone age = 1.61 ( chronological age ) ‐0.04(chronological age)2 ‐ 3.61 . This equation was used to correct adult height predictions . The median initial dose of GH  was 0.8 IUkglweek and was maintained during the first 3 years of treatment . The median frequency of injections was six/week . Height velocity increased from 4.1 to 6.8 cm/year in the first year , and height velocity SDS for chronological age remained positive for 4 years . The height prediction corrected for bone age increased over the first 2 years only . Differences in demography and auxology were described according to karyotype and country of origin . A greater height velocity SDS was observed at higher GH doses and when ox and rolone was used concomitantly
AUTHORS ' CONCLUSIONS Addition of ox and rolone to the GH therapy led to a modest increase in the final adult height of girls aged up to 18 years with TS .
BACKGROUND The final adult height of untreated girls aged up to 18 years with Turner syndrome ( TS ) is approximately 20 cm shorter compared with healthy females .
Treatment with growth hormone ( GH ) increases the adult height of people with TS .
The effects of adding the and rogen , ox and rolone , in addition to GH are unclear .
Therefore , we conducted this systematic review to investigate the benefits and harms of ox and rolone as an adjuvant therapy for people with TS treated with GH .
OBJECTIVES To assess the effects of ox and rolone on growth hormone-treated girls aged up to 18 years with Turner syndrome .