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Short-term effects of follicle-stimulating hormone on immune function, lipid, and vitamin metabolism in transiently castrated men

Guedes, Jéssica LU ; Pla, Indira LU orcid ; Sanchez, Aniel LU ; Marko-Varga, Gyorgy LU ; Domont, Gilberto Barbosa ; Sahlin, K. Barbara ; Hazir, Berk LU orcid ; Giwercman, Aleksander LU ; Nogueira, Fábio César Sousa LU and Malm, Johan LU , et al. (2025) In Endocrine Connections 14(2).
Abstract

Background: Prostate cancer therapy with surgical or chemical castration with gonadotropin-releasing hormone (GnRH) agonists has been linked to elevated follicle-stimulating hormone (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... (More)

Background: Prostate cancer therapy with surgical or chemical castration with gonadotropin-releasing hormone (GnRH) agonists has been linked to elevated follicle-stimulating hormone (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 (300 IU 3 times/week) for 5 weeks, while seventeen men served as controls. After 3 weeks, all men received 1000 mg intramuscular testosterone undecanoate. 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). In addition, 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 extragonadal systems and its connection to metabolic disorders often seen as secondary effects of prostate cancer treatment.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
GnRH agonist, GnRH antagonist, gonadotropins, metabolomics, molecular profiling, prostate cancer, proteomics
in
Endocrine Connections
volume
14
issue
2
article number
e240587
publisher
BioScientifica
external identifiers
  • pmid:39745472
  • scopus:85217066754
ISSN
2049-3614
DOI
10.1530/EC-24-0587
language
English
LU publication?
yes
id
b01565f1-4bd8-4719-9d30-1e516b9ec0e8
date added to LUP
2025-04-02 13:21:12
date last changed
2025-06-11 18:20:07
@article{b01565f1-4bd8-4719-9d30-1e516b9ec0e8,
  abstract     = {{<p>Background: Prostate cancer therapy with surgical or chemical castration with gonadotropin-releasing hormone (GnRH) agonists has been linked to elevated follicle-stimulating hormone (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 (300 IU 3 times/week) for 5 weeks, while seventeen men served as controls. After 3 weeks, all men received 1000 mg intramuscular testosterone undecanoate. 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). In addition, low FSH levels were correlated with a reduction in the active form of vitamin D (P &lt; 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 extragonadal systems and its connection to metabolic disorders often seen as secondary effects of prostate cancer treatment.</p>}},
  author       = {{Guedes, Jéssica and Pla, Indira and Sanchez, Aniel and Marko-Varga, Gyorgy and Domont, Gilberto Barbosa and Sahlin, K. Barbara and Hazir, Berk and Giwercman, Aleksander and Nogueira, Fábio César Sousa and Malm, Johan and Giwercman, Yvonne Lundberg}},
  issn         = {{2049-3614}},
  keywords     = {{GnRH agonist; GnRH antagonist; gonadotropins; metabolomics; molecular profiling; prostate cancer; proteomics}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{BioScientifica}},
  series       = {{Endocrine Connections}},
  title        = {{Short-term effects of follicle-stimulating hormone on immune function, lipid, and vitamin metabolism in transiently castrated men}},
  url          = {{http://dx.doi.org/10.1530/EC-24-0587}},
  doi          = {{10.1530/EC-24-0587}},
  volume       = {{14}},
  year         = {{2025}},
}