Salutary effects of combining early very low-dose systemic estradiol with growth hormone therapy in girls with Turner syndrome.
BACKGROUND
Optimizing pubertal estrogen replacement in girls with Turner syndrome is important.


OBJECTIVE
The study objective was to test the hypotheses that physiological estradiol replacement administered early with GH will preserve height potential as much as if administered late and that it will bring about a greater height gain than standard oral estrogen therapy combined with GH.


METHODS
The study was randomized to early or late estrogen treatment; follow-up was at 3.5 yr or later.


METHODS
This was a multicenter outpatient study.


METHODS
Turner syndrome girls 12.0-12.9 yr (n = 7) or 14.0-14.9 yr (n = 7) of age who began GH before age 12.0 yr were the patients. The girls were matched to National Cooperative Growth Study registry patients who began GH and oral conjugated estrogen at similar ages and were similarly followed to adult or near-adult height.


METHODS
Depot estradiol, 0.2 mg/month i.m., was given initially and gradually increased; GH was 0.05 mg/kg daily.


METHODS
Adult or near-adult height was the main outcome variable.


RESULTS
Depot estradiol treatment resulted in height significantly taller than predicted at 12 yr of age (P < 0.02). All height potential was gained in the first 2 yr of the study, during which the early group grew 3.5 cm more than the late group, which was receiving GH alone (P < 0.01). The early depot estradiol group also gained 5.9 cm more height after starting estrogen than did the early National Cooperative Growth Study group (P < 0.05). Although feminization proceeded slowly on the lowest dose of estradiol, it advanced normally thereafter.


CONCLUSIONS
These results suggest that very low-dose parenteral estradiol permits relatively age-appropriate feminization without interfering with the effect of GH on the enhancement of height potential.
Rosenfield
Robert L
RL
The University of Chicago Pritzker School of Medicine, Chicago, Illinois 60637, USA. robros@peds.bsd.uchicago.edu
Devine
Nancy
N
Hunold
Joanne Julius
JJ
Mauras
Nelly
N
Moshang
Thomas
T
Root
Allen W
AW
D001827:Body Height / Q000187:drug effects; D001940:Breast / Q000254:growth & development; D002648:Child; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D013006:Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007273:Injections, Intramuscular; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008572:Menarche / Q000187:drug effects; D014424:Turner Syndrome / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology
D003692:Delayed-Action Preparations; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D005640:Follicle Stimulating Hormone; D013006:Growth Hormone