Context: The impact of long-term GH replacement on cerebral- and cardiovascular diseases and diabetes mellitus (DM) in hypopituitary patients is unknown.

Objective: The incidence of non-fatal stroke and cardiac events, and prevalence of type 2 DM (T2D) and cardioprotective medication were compared between cohorts of GHD patients and population controls.

Design and Participants: The incidence of non-fatal stroke and cardiac events was estimated retrospectively from questionnaires, in 750 GHD patients and 2,314 matched population controls. Prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 years and time on GH therapy was 6 years for GHD women and men, respectively.

Results: Lifelong incidence of non-fatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency (FHD) and GH deficiency (GHD), during which most patients had GH therapy. Lifelong incidence of non-fatal cardiac events declined in GHD men during FHD- and GHD-periods. GHD women had higher prevalence of T2D and lipid-lowering medication, whereas GHD men had higher prevalence of antihypertensive medication.

Conclusions: The declined risks of non-fatal stroke in both gender and of non-fatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6 years of GH replacement. GHD women had increased prevalence of T2D, partly attributed to higher BMI and lower physical activity.