Patients and methods
ADVERSE EVENTS, ADVERSE EVENT, BLOOD
Four patients had a TV of 3 ml but had elevated morning testosterone values (i.e., 1.4, 1.3, 1.8, and 2 nmol/L) and were included. One patient had a TV of 2 ml and a morning testosterone value of 0.6 nmol/L; the GnRH test showed pubertal values.The boys were examined by study doctors twice before the study, at inclusion, and after 3, 6, and 12 months. The patients were seen by study nurses at inclusion, for injections, and for blood tests on days 0, 2, 7, 30, 60, 90, 180, and 365. Weight, height, and blood pressure measurements were made using the standard instruments at the pediatric clinic. All visits to the clinic were between 07:30 and 09:00 a.m. Data were recorded in case report forms, and an independent monitor from the Sahlgrenska Center for Pediatric Ophthalmology Research at the University of Gothenburg surveilled PRIBS. Adverse events and severe adverse events were recorded.Boys randomized to TE received six monthly 0.3-ml i.m. injections, each containing 75 mg of TE (250 mg/ml); boys randomized to TU received one 1-ml i.m. injection containing 250 mg of TU (1,000 mg/4 ml) twice, 3 months apart. In PRIBS, the nurses administered the intramuscular testosterone injections, and the medication vials/cartridges were slowly turned up and down 20 times before injection.LH, FSH, and testosterone levels were evaluated twice before the study start and after 3, 6, and 12 months. Morning testosterone was also evaluated twice before the study start on days 0, 2 and 7 and after 1, 2, 3, 6, and 12 months. Inhibin B was analyzed during the study start and after 12 months. Hb, liver enzymes, pulse, blood pressure, height, and weight were measured before the study start and after 0, 3, 6, and 12 months during the study as a safety measure. Health-related quality of life was assessed during the study start and after 6 and 12 months. Blood samples have been frozen for future analysis of 17β-estradiol (using mass spectrometry), sex hormone-binding globulin (SHBG), and anti-Müllerian hormone (AMH).