Introduction
ADVERSE EFFECTS, HYPOGONADISM, DELAYED PUBERTY
At puberty, male sexual differentiation restarts with nightly pulsatile stimulating impulses of hypothalamic gonadotropin-releasing hormone (GnRH) to the pituitary gland, which releases luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (If puberty does not start at age 14 years, it can be delayed or absent (i.e., hypogonadism). Absent puberty (i.e., hypogonadotropic hypogonadism) is a difficult diagnosis to make unless the patient is 18 years old and has not started puberty. Clinically, patients investigated for delayed puberty can also present slowly progressing puberty with a testis volume of 4–6 ml and early pubertal levels of morning testosterone without increased growth velocity (In Sweden, boys with delayed or slowly progressing puberty are treated (if they want medication) with testosterone enanthate (TE) (Testoviron DepotAlthough we have long clinical experience with TE, it has not been evaluated in clinical trials for children. Although TE treatment is off-label and has not been fully evaluated, it has become the standard of care (SoC) due to the convenience of the injection and because the treatment is considered well-tolerated. Newer testosterone treatment options, such as long-acting testosterone undecanoate (TU) (NebidoOther treatment options for pubertal development, such as methyl testosterone implants, topical solutions, and oral tablets, are seldom used in Sweden for fear of adverse effects and because of difficulty administering and monitoring the resulting testosterone levels (TE is only available on license in Sweden. TE was deregistered in Sweden in 2006 and is not available on regular drug prescriptions and can only be obtained The study was initiated to compare the two products on pubertal progression. Our research hypothesis was that long-acting testosterone administered every 3 months would not be inferior to monthly injections of traditional testosterone for pubertal development. This hypothesis was based on a few observations by the investigators of long-acting TU in doses of 1/4–1/5 of the adult dose, used for pubertal replacement therapy.