Background Severe congenital hypogonadotropic hypogonadism (CHH) in boys can be diagnosed during the minipuberty of infancy. Combined gonadotrophin treatment at that age is suggested to improve testicular function, yet long-term evidence is lacking. We describe the first long-term follow-up data on CHH boys treated with recombinant human follicle stimulating hormone [r-hFSH] as infants. Patients and Methods This is a retrospective patient chart review of five boys from two pediatric tertiary centers in Finland (2004-2016). Four patients had panhypopituitarism of yet unknown etiology, one had CHARGE syndrome due to a CHD7 mutation. The patients were treated at the age of 0.7 to 4.2 months with r-hFSH (from 16.6 IU to 33.4 IU s.c. per week for 3 to 4.3 months) combined with testosterone [T] (25 mg i.m. monthly for three months). Inhibin B levels and testicular development were followed for 1.9 to 12.2 years after the treatment. Results During the r-hFSH + T treatment, inhibin B increased from 76 ± 18 ng/L to 176 ± 80 ng/L (p = 0.04) and penile length increased by 81 ± 50% (p = 0.04). All boys underwent orchidopexy at 2.0 ± 0.7 years of age; one boy had testicular regression. Unexpectedly, two boys with robust inhibin B responses in infancy demonstrated low inhibin B values in peripuberty: from 290 ng/L (4 months) to 16 ng/L (12.4 years), and from 207 ng/L (6 months) to 21 ng/L (12.8 years). Conclusions This is the first report of the long-term effects of r-hFSH-treatment given during minipuberty. The data suggest that Sertoli-cell response to r-hFSH is transient and that testosterone, given concomitantly with r-hFSH at infancy, does not inhibit Sertoli cell activity. Our observations require confirmation from larger longitudinal patient series.