title: A randomized trial of transdermal and oral estrogen therapy in adolescent girls with hypogonadism.
abstract: BACKGROUND
  Adolescent females with ovarian failure require estrogen therapy for induction of puberty and other important physiologic effects. Currently, health care providers have varying practices without evidence-based standards, thus investigating potential differences between oral and transdermal preparations is essential. The purpose of this study was to compare the differential effects of treatment with oral conjugated equine estrogen (OCEE), oral 17β estradiol (OBE), or transdermal 17β estradiol (TBE) on biochemical profiles and feminization in girls with ovarian failure.
  
  
  METHODS
  20 prepubertal adolescent females with ovarian failure, ages 12-18 years, were randomized to OCEE (n = 8), OBE (n = 7), or TBE (n = 5) for 24 months. Estrogen replacement was initiated at a low dose (0.15 mg OCEE, 0.25 mg OBE, or 0.0125 mg TBE) and doubled every 6 months to a maximum dose of 0.625 mg/d OCEE, 1 mg/d OBE, or 0.05 mg/d TBE. At 18 months, micronized progesterone was added to induce menstrual cycles. Biochemical markers including sex hormones, inflammatory markers, liver enzymes, coagulation factors, and lipids were obtained at baseline and 6 month intervals. Differences in levels of treatment parameters between the groups were evaluated with one-way analysis of variance (ANOVA). The effect of progesterone on biochemical markers was evaluated with the paired t-test.
  
  
  RESULTS
  Mean (±SE) estradiol levels at maximum estrogen dose (18 months) were higher in the TBE group (53 ± 19 pg/mL) compared to OCEE (14 ± 5 pg/mL) and OBE (12 ± 5 pg/mL) (p ≤ 0.01). The TBE and OBE groups had more effective feminization (100% Tanner 3 breast stage at 18 months). There were no statistical differences in other biochemical markers between treatment groups at 18 months or after the introduction of progesterone.
  
  
  CONCLUSIONS
  Treatment with transdermal 17β estradiol resulted in higher estradiol levels and more effective feminization compared to oral conjugated equine estrogen but did not result in an otherwise different biochemical profile in this limited number of heterogeneous patients. OBE and TBE provide safe and effective alternatives to OCEE to induce puberty in girls, but larger prospective randomized trials are required.
  
  
  BACKGROUND
  
  
  
  BACKGROUND
  NCT01023178.
authors: Division of Pediatric Endocrinology and Diabetes, Stanford University, Stanford CA (S.S., E. D., E.N.), 300 Pasteur Drive, G-313, 94305 Stanford, CA, USA.
authors: Sejal
authors: S
authors: Shah
authors: Pediatric Endocrinology and Diabetes, Children's Hospital of Orange County, Orange CA (N.F.), 1201 W La Veta, 92868 Orange, CA, USA.
authors: Nikta
authors: N
authors: Forghani
authors: Division of Pediatric Endocrinology and Diabetes, Stanford University, Stanford CA (S.S., E. D., E.N.), 300 Pasteur Drive, G-313, 94305 Stanford, CA, USA.
authors: Eileen
authors: E
authors: Durham
authors: Division of Pediatric Endocrinology and Diabetes, Stanford University, Stanford CA (S.S., E. D., E.N.), 300 Pasteur Drive, G-313, 94305 Stanford, CA, USA.
authors: E Kirk
authors: EK
authors: Neely
keywords: Clinical trial; Estrogen; Female; Feminization; Hormone replacement therapy; Puberty