Background: Prostate cancer therapy with surgical or chemical castration with GnRH agonists has been linked to elevated FSH levels, which may contribute to secondary health disorders, including atherosclerosis and diabetes. Although recent findings suggest a role for FSH beyond the reproductive system, its metabolic impact remains unclear and difficult to disentangle from that of androgens. In this study, we examined the metabolic changes induced by FSH and distinguished them from those caused by testosterone.
Methods: Plasma samples from temporarily medically castrated young men (n=33) treated with FSH and/or testosterone were characterized by proteomics and metabolomics approaches. All subjects received GnRH antagonists. Sixteen men were randomized to recombinant FSH (rFSH, 300 IU 3 times/week) for 5 weeks, while seventeen men served as controls. After 3 weeks, all men received 1000 mg testosterone undecanoate intramuscular. Blood samples were collected at the start, after 3 weeks, and after 5 weeks. The proteome and metabolome signatures were characterized in all samples.
Results: FSH significantly upregulates key proteins involved in the modulation of inflammatory response and innate immune system (p≤0.03) and dysregulates lipid metabolism, evidenced by downregulation of multiple apolipoproteins (p≤0.04) and increased levels of cholesterol and glycerophospholipids (p≤0.03). Additionally, low FSH levels were correlated with a reduction in the active form of vitamin D (p<0.02). These results highlight the short-term metabolic impacts of FSH in males.
Conclusions and clinical implications: Our findings underlined the FSH effect on extra-gonadal systems and its connection to metabolic disorders often seen as secondary effects of prostate cancer treatment.