Physiological Estrogen Replacement Therapy for Puberty Induction in Girls: A Clinical Observational Study

Abstract

Background/Aim: The goal of estrogen replacement therapy (ERT) in girls with hypogonadism is to achieve the endocrine milieu similar to natural puberty, where transdermal administration is the most physiological route. The aim of the study was to evaluate guidelines for the induction of puberty with transdermal estradiol (E₂) patches in a large outpatient setting. Methods: In a retrospective study, serum E₂ levels from 18 clinics were analyzed at the Göteborg Pediatric Growth Research Center laboratory, as part of the initiation of ERT in girls with hypogonadism. Exclusion criteria were pubertas tarda and pubertal arrest. Eighty-eight observations (50 with Turner syndrome, TS) were included. Serum E₂ levels were determined by extraction + radioimmunoassay (detection limit 4 pmol/l) and analyzed in relation to the dose of Evorel® (25 µg/24 h, containing 1.60 mg estradiol hemihydrate; Janssen-Cilag Pharmaceutica N.V., Beerse, Belgium). Results: There was a linear relationship between serum E₂ and the weight-based dose, with r = 0.56, p < 0.0001 for all observations and r = 0.59, p < 0.0001 for the TS study group. Linear regression analysis for doses of 0.05-0.07 µg/kg resulted in serum levels of 17-23 pmol/l (TS 17-24 pmol/l) and doses of 0.08-0.12 µg/kg in 26-39 pmol/l (TS 27-39 pmol/l). Conclusions: For the initiation of ERT with nocturnally administered E₂ patches, we recommend reduced starting doses of 0.05-0.07 µg/kg, with the goal of mimicking E₂ levels during gonadarche. In older girls, when breast development is of high priority, the starting dose can still be 0.08-0.12 µg/kg.

17β-Estradiol and Gonadotropin Levels for the Diagnosis of the Benign Form of Breast Development in Girls Aged up to 4 Years in Real-Life Clinical Practice

“…It is presented in Figure 4. The 17β-E2 ranges were chosen from reference values from prepubertal girls and girls in early puberty from the laboratory analysing current samples [20]. The girls are divided into the following 4 groups:…”

European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment

“…In older girls, when breast development is a high priority, the starting dose of transdermal estradiol can be 0.08-0.12 μg/kg. 217 The estradiol dose is slowly increased over 12-24 months, after which time cyclic gestagen is added (or after the first menstrual bleed) in order to maximize breast development. In adulthood, estradiol is typically given orally (at a dose of 1-2 mg) or transdermally (50 μg daily by patch or 1-2 pumps of 0.06% gel daily) as a maintenance dose with a cyclic progestin regimen (progesterone 200 mg for 14 days of the cycle, depending on formulation) to avoid endometrial hyperplasia.…”

Optimal Pubertal Induction in Girls with Turner Syndrome Using Either Oral or Transdermal Estradiol: A Proposed Modern Strategy

“…While transdermal estradiol treatment has strong theoretical advantages over oral treatment and has been used in Sweden for decades [15], the evidence for any superiority is lacking. Matthews et al [13] write, “There is a real paucity of carefully constructed, randomised controlled clinical trials in girls undergoing induction of puberty.…”