A randomized trial of transdermal and oral estrogen therapy in adolescent girls with hypogonadism
Open accessAbstract
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. STUDY DESIGN: 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. CLINICAL TRIALS IDENTIFIER: NCT01023178.
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Transdermal E2 led to more effective feminization after 2 years compared with oral conjugated equine estrogen.
“TD E2 led to more effective feminization after 2 years compared with oral conjugated equine estrogen.”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [318]
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- Authors
- Shah, S., Forghani, N., Durham, E., & Neely, E. K.
- Affiliations
- Stanford Medicine (US)
- Children's Hospital of Orange County (US)
- Corresponding author
- Shah, Sejal
- Venue
- International Journal of Pediatric Endocrinology
- Published
- 2014-06-20
- Volume
- 2014
- Issue
- 1
- Pages
- 12-12
- ISSN
- 1687-9848 (ISSN-L)
- 1687-9856
- PMC
- PMC4074834
- OpenAlex
- W2097893186
- Cited by
- 32
- References
- 27
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 7 · 2017: 2 · 2016: 1 · 2015: 5
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- International Journal of Pediatric Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Center for Research Resources (UL1RR025744)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- transdermal estradiol, oral estradiol, conjugated equine estrogens, ovarian failure, adolescent girls, puberty induction, feminization, breast development, estradiol levels, progesterone, estrogen replacement therapy, inflammatory markers, liver enzymes, lipids, coagulation factors, treatment safety and efficacy comparison
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