ESPEYB20 7. Oncology and Chronic Disease Gonadal Function and Fertility Issues in Childhood Cancer Survivors (7 abstracts)
7.2. Towards an individualized management of pubertal induction in girls with hypogonadism: insight into the best replacement outcomes from a large multicentre registry
Rodari G , Federici S , Todisco T , Ubertini G , Cattoni A , Pagano M , Giacchetti F , Profka E , Citterio V , Messetti D , Collini V , Soranna D , Carbone E , Arosio M , Mantovani G , Persani L , Cappa M , Bonomi M & Giavoli C
m.bonomi@auxologico.it Eur J Endocrinol. 2023; 188(6):467–476. doi: 10.1093/ejendo/lvad056. PMID: 37232247.
Brief summary: This longitudinal observational multicentre retrospective study, collected data on 95 young prepubertal or early pubertal girls (age >10.9 years, Tanner stage ≤2) with premature ovarian failure (POI) or hypogonadotropic hypogonadism (HH). Their hypogonadism was due to different causes and was treated with transdermal 17β-oestradiol, with a follow-up of at least 1 year. The study aimed to identify the most physiological and effective therapeutic scheme.
The study population was divided according to the cause of puberty failure: cancer treatment (CancerHH or CancerPOI), congenital isolated forms of hypogonadotropic hypogonadism (CHH), multiple pituitary hormone deficiency (MPHD), Turner syndrome spectrum (TS), and secondary POI. Despite some differences in the pubertal induction approach between the 4 participating centres, Tanner stage B5 was reached only in 41% of patients who completed pubertal induction, and it was significantly associated with transdermal 17β-oestradiol dose at progesterone introduction and number of dose changes. Uterine longitudinal diameter (ULD) was suboptimal in >50% of patients. Mean ULD was shorter in the CancerPOI group, despite no difference in the induction regimens used. In the same group, the uterus had also less frequently an adult shape. Pelvic irradiation, in the context of total body-irradiation or pelvic radiotherapy, was the major determinant of impaired ULD, probably as a result of radiation-induced vascular damage and uterine fibrosis.
Final ULD was not significantly different from the ULD at the time of progesterone introduction and was related to oestrogen levels. The authors suggest to perform a pelvic ultrasound before starting progesterone, rather than introduce this hormone after the first vaginal bleeding, as is usually advised. In girls with small ULD at ultrasound, oestrogen therapy should be extended or increased before progesterone introduction to reach more appropriate uterine size and shape. However, this approach may be not recommended in poor responders with CancerPOI, whose uterine growth might be restricted by pre-existing damage, and in whom the risk of adverse effects related to high oestrogen doses may be more concerning.
Another aim of pubertal induction is to reach an adult height compatible with mid-parental height. As expected, in this study adult height was lower than mid-parental height in TS and CancerPOI groups.
There is still no agreement on the optimal protocol for pubertal induction, particularly with regard to the combination of oestrogen and progesterone and the timing of progesterone introduction, to ensure adequate breast and uterine development and prevent endometrial hyperplasia. Breast and uterine development are considered crucial both for self-esteem and future opportunity of pregnancy, in patients who already have reduced quality of life due to the disease itself. Despite the limitations due to its retrospective design, the sample size of this study is large, and the results provide innovative messages that will be useful for clinical management of girls requiring pubertal induction.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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