ECE2022 Rapid Communications Rapid Communications 12: Reproductive and Developmental Endocrinology (8 abstracts)
Pubertal induction in girls with hypogonadism: insight into estrogen replacement therapy outcomes and optimization of progesterone introduction
Giulia Rodari 1 , Silvia Federici 2,3 , Alessandro Cattoni 4 , Tommaso Todisco 5 , Graziamaria Ubertini 5 , Federico Giacchetti 6 , Eriselda Profka 6 , Alberta Dall’Antonia 7 , Biagio Cangiano 2,3 , Maura Arosio 1,6 , Marco Bonomi 2,3 , Marco Cappa 5 & Claudia Giavoli 1,6
1University of Milan, Department of Clinical Sciences and Community Health, Milan, Italy; 2University of Milan, Department of Medical Biotechnology and Translational Medicine, Milan, Italy; 3IRCCS Istituto Auxologico Italiano, Dept. of Endocrine and Metabolic Diseases and Lab. of Endocrine and Metabolic Research, Milan, Italy; 4Fondazione MBBM, San Gerardo Hospital, Department of Pediatrics, Università degli studi di Milano-Bicocca, Monza, Italy; 5University-Hospital Pediatric Department (DPUO), Bambino Gesù Children’s Hospital, IRCCS, Endocrinology Unit, Rome, Italy; 6Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy; 7University of Milan, Milan, Italy
Background: Pubertal induction in girls with hypogonadism through estrogen replacement therapy (ERT) aims at mimicking physiological puberty. To date, the best induction regimen is still to be established.
Aims: By setting up a multicentre clinical registry, we analysed longitudinal data on pubertal induction in girls with hypogonadotropic hypogonadism or premature ovarian insufficiency (congenital, acquired, isolated or associated with multiple pituitary hormone deficiency, either associated with Turner Syndrome or secondary to late effects of cancer treatment) in order to insight into auxological and uterine outcomes in the light of different underlying diagnosis and regimens used.
Methods: Out of 106 hypogonadal girls (chronological age>10.9 years, Tanner stage ≤ 2) who received ERT for pubertal induction included in the register, we considered 95 girls (median age 13.5 years) treated with transdermal (TD) 17β-estradiol patches for at least one year (median 3.3 years). Induction was started at a median dose of 0.14 mg/kg/day TD 17β-estradiol, with a six-monthly increase. Auxological, biochemical (estradiol levels) and radiological (pelvic US) data were collected at baseline and during follow-up. In 61/95 girls, progesterone was introduced after a median of 2.2 years. Induction was considered completed for the 49/95 patients who were started on combined oral contraceptive (COC) or progesterone plus at least 50 mg/day or 1 mg/kg/day of TD 17β-estradiol.
Results: at the end of induction, 90.0% patients had achieved Tanner stage B4 and 41.0% B5, the latter being associated with 17β-estradiol dose at progesterone introduction ( P=0.034). Uterine longitudinal diameter (ULD) showed a gradual increase during ERT and a significant correlation with 17β-estradiol dosage (P<0.0001) at any point of induction. Nonetheless, final ULD was>65 mm in only 17/45 (38%). At multiple regression analysis, a history of pelvic irradiation represented the major determinant of reduced final ULD (P=0.034). After correction for uterine irradiation and other clinical confounders, ULD was associated with 17β-estradiol dose at progesterone introduction (P=0.043). Final ULD was not significantly different from the one assed after COC introduction.
Conclusions: reaching an appropriate 17β-estradiol dose at the end of the induction seems to play a crucial role in uterine development and Tanner stage 5 achievement. Indeed, progesterone should be started only in the presence of a concomitant adequate ERT dose and an appropriate uterus and breast development, given the evidence that progestins may hamper the subsequent changes in uterus volume or the achievement of the last Tanner stage. At present, we aim to confirm present results on a larger scale.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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