Background: The Turner Syndrome Life Course Project, UCLH, has collected data on 810 women with TS, attending clinic for 20 years and has accumulated over 8000 clinic visits. We present an analysis of the effects of timing and type of exogenous oestrogen on health outcomes in adults.
Methods: A cross- sectional analysis of 475 subjects with primary amenorrhoea with accurate age of pubertal induction data was performed using correlation coefficients controlling for age.
A second univariate analysis inclusive of individuals with secondary amenorrhea, using data from 5225 clinic visits was performed to assess the effect of oestrogen type on medical endpoints. Age and BMI were controlled for. Hormone replacement therapies (HRT) were categorised as combined oral contraceptive (OCP; n=1526) clinic visits, oral oestrogens (combined 17B estradiol and conjugated equine oestrogens; n=3036) and transdermal 17B estradiol (n=663).
Results: Median (90th centiles) age of pubertal induction was 14 years. Oestrogen start age correlated with hip and spine T-score (P=<0.01). Differences in medical endpoints for three types of HRT included raised liver enzymes (AlkP, ALT, GGT) associated with transdermal estradiol compared to oral oestrogens and OCP users (P=<0.01). Blood pressure was elevated in the OCP users compared to oral and transdermal oestrogen users (P=< 0.01). Bone density was greater in transdermal estradiol users compared to OCP and oral oestrogens users (P=< 0.01).
Conclusions: An earlier oestrogen start age was associated with greater bone density. This data supports an earlier age of pubertal induction before age 14.
Whilst bone density was greater in transdermal users, this group also experience elevated liver enzyme parameters. Therefore there may be a trade off when considering oral versus transdermal in the management of TS.
OCP users experience higher blood pressure. Given the propensity of women with TS to develop hypertension ethinylestradiol is contraindicated.