Induction of puberty in hypogonadal forms of primary amenorrhoea: current evidence and future perspectives.

Primary amenorrhoea is defined as the absence of spontaneous menarche by the age of 15 years with normal pubertal development or of 13 years in the absence of pubertal signs. The aim of this review was to provide a comprehensive overview of current evidence on puberty induction in girls with primary amenorrhoea, to highlight clinical practices, and to identify directions for future research. Puberty induction aims not only to achieve secondary sexual characteristics but also to ensure an appropriate growth spurt and attainment of final adult height, optimal peak bone mass achievement, uterine development and maturation, and psychosocial well-being. Oestrogen therapy (preferably oral or transdermal 17β-oestradiol), initiated at low doses and gradually increased, remains the cornerstone of treatment for girls with absent or arrested puberty. Progesterone is usually introduced after 18-24 months or following spontaneous bleeding to prevent endometrial hyperplasia, although timing should be individualized according to uterine response to oestrogen. Clinical evidence indicates that premature progestin introduction should be avoided to allow complete uterine and breast development; therefore, a patient-centred approach tailored to individual characteristics is essential. Moreover, reproductive technologies have expanded fertility options for women with either central hypogonadism or premature ovarian insufficiency. In this context, a tailored approach aimed at achieving optimal uterine development is crucial. Most available data derive from Turner syndrome cohorts and small observational studies, underscoring the need for individualized protocols. Importantly, future research should further investigate bone metabolism and psychosocial aspects, with the goal of refining clinical practice in pubertal induction.