The homeo-FIT-prolactin hypothesis: the role of prolactin in metabolic homeostasis - association or causality?

The homeo-fit-prolactin hypothesis proposes a causal metabolic role for prolactin with hypoprolactinemia and hyperprolactinemia leading to adverse metabolic alterations. However, prolactin within the normal range and up to four times the upper reference limit may be a consequence of metabolic adaption and have a positive metabolic role similar to increased insulin in pre-diabetes. As a consequence, drugs that would increase prolactin levels within this threshold may hold promising effects, particularly for patients with type 2 diabetes. A documented positive metabolic effect of prolactin just above the normal threshold would not just be of benefit to patients with diabetes but assist in the decision to treat mild hyperprolactinemia in other patient groups as well, e.g. drug-induced hyperprolactinemia or idiopathic hyperprolactinemia. Prolactin receptors are present in the pancreas, liver, and adipose tissue, and pre-clinical studies suggest a positive and causal effect of prolactin on the gluco-insulinemic profile and lipid metabolism. This narrative review examines the evidence for the homeo-fit-prolactin hypothesis with a particular focus on results from human studies.