Methods: To further explore the relationship between FSH and ADT unwanted effects, a panel of world key opinion leaders in the treatment of prostate cancer was convened, and a review of the literature in Medline and PubMed was conducted.
Results: Several potential mechanisms mediated by FSH which may contribute to adverse musculoskeletal effects were identified. FSH stimulates osteoclastogenesis by promoting the expression of receptor activator of nuclear factor-kappaB (RANK) on osteoclast precursor cells, as well as the activation of RANK through the stimulation of RANK-ligand secretion. FSH also promotes the release of tumor necrosis factor (TNF)-α from mononuclear cells, which likewise differentiates precursors cells into osteoclasts. Additionally, osteoclast survival time was shown to increase following FSH-mediated stimulation of interleukin (IL)-1β from monocytes, allowing ongoing promotion of bone resorption. Also, patients with bone metastases demonstrate increased concentrations of the bone resorption marker, N-telopeptide, which has been correlated with morbidity and mortality outcomes.
Conclusions: These findings suggest that possible undesired effects of ADT may be precipitated from the result of FSH escape. Additional research is required to confirm a causal relationship between the FSH pathway and the adverse effects associated with ADT.
Funding source: The studies reported were funded by Ferring Pharmaceuticals Inc.
E. David Crawford MD1, Andrew V. Schally PhD MDhc (Multi) D.Sc hc2*, John H. Hoenemeyer MD1, Neal D. Shore MD FACS CPI3, Phillip A. Saccone PhD4*, Thomas J. Beveridge PhD4*, Dennis C. Marshall RN MS PhD4*.
1Aurora, CO, 2Miami, FL, 3Myrtle Beach, SC, 4Parsippany, NJ.