Blood Rev. 2021; 45: 100730. https://pubmed.ncbi.nlm.nih.gov/32654893/
This practical treatment protocol was developed by an experienced multidisciplinary team following a critical and updated systematic review of the literature.
Hypogonadism is a common finding after antineoplastic treatment. It can either result from a primary gonadal disorder (due to pelvic irradiation and alkylating agents) or from hypothalamic-pituitary ovarian axis damage (due to cranial or craniospinal radiotherapy), or both. Hematopoietic stem cell transplantation (HSCT) is an independent risk factor for premature ovarian insufficiency (POI); the incidence of POI ranges from 44 to 100% among HSCT childhood recipients. Few studies have investigated iatrogenic POI in children and young adolescents (1).
The clinical approach described here was extrapolated from published evidence on adult women with POI due to multiple etiologies. In post-pubertal patients with incipient iatrogenic POI, if no contraception is requested, hormone replacement therapy via 17βE-based transdermal patches is strongly recommended as the first line approach. Combined oral contraceptives should be prescribed only in patients who wish for contraception as a priority. In girls presenting with pubertal delay and a hormonal picture consistent with hypergonadotropic (primary) hypogonadism following childhood cancer +/− HSCT, transdermal 17βE is the recommended first line to induce puberty. Puberty induction should be started between ages 1113 years, when FSH levels are > 10 U/l, in analogy with management of Turner Syndrome. Estrogen doses should be increased 6-monthly with the aim of completing pubertal development in ~2 years, as in normal girls. Progestin therapy should be added when the first menstrual bleed occurs.
Reference: 1. van Dorp W, et al. Recommendations for Premature Ovarian Insufficiency Surveillance for Female Survivors of Childhood, Adolescent, and Young Adult Cancer: A Report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in Collaboration with the PanCareSurFup Consortium. J Clin Oncol. 2016. PMID: 27458300