Effects of Estrogen Therapies on Outcomes in Turner Syndrome: Assessment of Induction of Puberty and Adult Estrogen Use

J Clin Endocrinol Metab. 2019 Jul 1;104(7):2820-2826. doi: 10.1210/jc.2018-02137.


Context: Turner syndrome (TS) is often associated with delayed puberty. To induce puberty, estrogen is administered in incremental doses at an age determined by age of presentation. After puberty, various types of maintenance estrogen replacement therapy (ERT) are used.

Objective: We sought associations between age of induction of puberty and type of ERT on adult health outcomes.

Design: Health surveillance data included blood profiles, bone density, and blood pressure. We assessed interactions between these data and age at first estrogen exposure in women with primary amenorrhea. We also assessed these data according to ERT subgroups [combined oral contraceptive pill (OCP), oral estrogen (OE), and transdermal estradiol (TE)] using data from each of 6679 clinic visits, controlling for age, body mass index, and height.

Setting: Adult TS clinic at University College London Hospital.

Patients: Of 799 women with TS, 624 had primary amenorrhea and 599 had accurate maintenance ERT data.

Main outcome measures: Parameters of health surveillance derived from clinical guidelines.

Results: Estrogen start age was negatively correlated with adult bone density (spine: r = -0.20 and hip: r = -0.022; P ≤ 0.001). OCP users had higher blood pressure and an adverse lipid profile compared with other ERT subgroups. TE was associated with elevated liver enzymes and hemoglobin A1c compared with OE (P ≤ 0.01).

Conclusions: An earlier age of induction of puberty may be beneficial for adult bone density. Given the high prevalence of hypertension in TS, the use of OCP for ERT should be limited. OE may be a benefit for steatohepatitis.

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Alanine Transaminase / metabolism
  • Alkaline Phosphatase / metabolism
  • Blood Pressure
  • Body Mass Index
  • Bone Density
  • Cholesterol / metabolism
  • Contraceptives, Oral, Combined / therapeutic use*
  • Estradiol / therapeutic use*
  • Estrogen Replacement Therapy / methods*
  • Estrogens / therapeutic use*
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Middle Aged
  • Puberty, Delayed / drug therapy*
  • Triglycerides / metabolism
  • Turner Syndrome / drug therapy*
  • Young Adult
  • gamma-Glutamyltransferase / metabolism


  • Contraceptives, Oral, Combined
  • Estrogens
  • Glycated Hemoglobin A
  • Triglycerides
  • hemoglobin A1c protein, human
  • Estradiol
  • Cholesterol
  • gamma-Glutamyltransferase
  • Alanine Transaminase
  • Alkaline Phosphatase