Relationship between circulating FSH levels and body composition and bone health in patients with prostate cancer who undergo androgen deprivation therapy. The BLADE study
Marco BergaminiAntonella VoltaCarlotta PalumboStefania ZamboniLuca TriggianiManuel ZampariniMarta LaganàLuca RinaudoNicola di MeoIrene CaramellaRoberto BrescianiFrancesca ValcamonicoPaolo BorghettiAndrea Emanuele GueriniDavide FarinaAlessandro AntonelliClaudio SimeoneGherardo MazziottiAlfredo Berruti
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Abstract Background Amongst its extragonadal effects, Follicle-Stimulating Hormone (FSH) has an impact on body composition and bone metabolism. Since androgen deprivation therapy (ADT) has a profound impact on circulating FSH concentrations, this hormone could potentially be implicated in the changes of fat body mass (FBM), lean body mass (LBM) and bone fragility induced by ADT. The objective of this study is to correlate FSH serum levels with body composition parameters, bone mineral density (BMD) and bone turnover markers at baseline conditions and after 12 months of ADT. Methods 29 consecutive non-metastatic prostate cancer (PC) patients were enrolled from 2017 to 2019 in a phase IV study. All patients underwent administration of the Luteinizing Hormone-Releasing Hormone antagonist degarelix. FBM, LBM and BMD were evaluated by dual-energy x-ray absorptiometry at baseline and after 12 months of ADT. FSH, alkaline phosphatase (ALP) and C-terminal telopeptide of type I collagen (CTX) were assessed at baseline and after 6 and 12 months. For outcome measurements and statistical analysis, T-test or sign test and Pearson or Spearman tests for continuous variables were used when indicated. Results At baseline conditions, a weak, non-significant, direct relationship was found between FSH serum levels and FBM at arms (r=0.36) and legs (r=0.33). Conversely, a stronger correlation was observed between FSH and total FBM (r=0.52, p=0.006), fat mass at arms (r=0.54, p=0.004) and fat mass at trunk (r=0.45, p=0.018) assessed after 12 months. On the other hand, an inverse relationship between serum FSH and appendicular lean mass index (ALMI)/FBM ratio was observed (r=0.64, p=0.001). This is an ancillary study of a prospective trial and this is the main limitation. Conclusions FSH serum levels after ADT could have an impact on body composition, in particular on fat body mass. Therefore, FSH could be a promising marker to monitor the risk of sarcopenic obesity and cardiovascular complications in PC patients undergoing ADT. Funding this research was partially funded by Ferring Pharmaceuticals. The funder had no role in design and conduct of the study, collection, management, analysis, and interpretation of the data and in preparation, review, or approval of the manuscript. Clinical trial number clinicalTrials.gov NCT03202381 , EudraCT Number 2016-004210-10.Keywords:
Bone remodeling
N-terminal telopeptide
The influence of ovine pituitary follicle-stimulating hormone (FSH) on the measurement of ovine pituitary luteinizing hormone (LH) in the ovarian ascorbic acid depletion (OAAD) and the ventral prostate weight (VPW) assays was examined. It was found that potentiation of ovine luteinizing hormone (NIH-LH-S1) was induced in the OAAD method by ovine follicle-stimulating hormone (NIH-FSH-Sl) when the latter hormone was present in sufficiently high concentration (FSH: LH =30:1 and 100:1). In the VPW assay, the activity of NIH-LH-Sl was not increased by ovine NIH-FSH-Sl at ratios of FSH:LH ranging from 1:1 to 30:1. (Endocrinology76: 1150, 1965)
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Radioimmunoassays for follicle stimulating hormone (FSH) and luteinizing hormone (LH) were used to determine the concentrations of these gonadotropins in sera from healthy men. No evidence of diurnal or other rhythmic variations in serum concentrations was found in samples obtained daily, 3 times a day, or hourly. Treatment of 3 subjects with 1.5 mg of ethinyl estradiol/day for 2–3 days resulted in a consistent fall in serum concentrations of both FSH and LH. Treatment of 3 subjects with 25 mg of testosterone propionate each day for 3 days resulted in a consistent fall in serum concentrations of LH. Treatment of 4 subjects with 200 mg of clomiphene citrate daily for 3 days resulted in a rise in serum concentrations of both FSH and LH.
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In boys with cryptorchidism median serum values of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are higher and median serum values of inhibin B lower than in normal controls. Serum values of inhibin B reflect the state of germinative epithelium in cryptorchid testes. The aim of the study was to evaluate whether a simple blood sample of gonadotropins and inhibin B could diagnose bilateral vanished testes.Group I included five boys (4 months to 6 years and 3 months old) with bilateral vanished testes at laparoscopy. Group II included 82 boys with bilateral cryptorchidism younger than 7 years of age at surgery for bilateral cryptorchidism (median age 1 year and 9 months).The serum levels of hormones for the patients with vanished testes were: inhibin B 5?18 pg/ml, FSH 41-191 IU/l and LH 3.9?56 IU/l. The patients all had karyotype 46,xy. The serum levels of hormones from group II were: inhibin B median 122 (range 20?404) pg/ml, FSH median 0.8 (range 0.2?3.5) IU/l and LH median 0.2 (range 0.1-3.2) IU/l. The serum levels of inhibin B, FSH and LH from the boys with vanished testes were significantly different from the serum levels of the boys with bilateral cryptorchidism (p = 0.0026, p < 0.0001 and p < 0.0001, respectively).The serum values of gonadotropins and inhibin B from boys with bilateral vanished testes were significantly different from those of bilateral cryptorchid boys, indicating no germinative epithelium, no Sertoli cells and compensatory high gonadotropins. If such abnormal serum values are obtained from boys with bilateral non-palpable testes, tubular tissue is not present and surgery can be avoided.
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Serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined by radioimmunoassay in 6 subjects who had been exposed accidentally to 192Ir gamma rays. All subjects showed normal levels of LH and FSH shortly after the irradiation. From 100 to 150 days post-irradiation, however, serum FSH levels increased in subjects who received 12.2 rad or more, a finding in agreement with the decrease in sperm concentration below 10 millions/ml, while in the other 2 subjects who received 9.8 and 10.9 rad, it remained within normal range. The elevation in serum FSH levels in one of the severely exposed subjects (Y. S.) was noted as late as 413 days after the exposure, while the hormone levels in the all other cases declined toward normal level.
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Summary: The biological and immunological activities of luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the serum of infertile males were determined by radioreceptor (RRA) and radioimmunoassay (RIA), respectively. In some sera the biological activity of serum LH was lower than expected on the basis of the RIA-data. In contrast, some sera contained unusually high levels of biologically active LH as demonstrated by RRA, despite not being detected in these amounts by RIA. Prolonged exposure of the gonad to such high levels of biologically active LH might cause end-organ desensitization resulting in infertility. The detection of such cases by the use of RRA could permit therapy in these individuals or exclude patients from treatment. Zusammenfassung: Vergleich der biologischen und immunologischen Aktivitäten des luteinisierenden und des follikelstimulierenden Mormons aus dem Serum infertiler Männer Die biologischen und immunologischen Aktivitäten des luteinisierenden Hormons (LH) und des follikelstimulierenden Hormons (FSH) im Serum infertiler Männer wurden durch Radiorezeptor-Assay (RRA) und Radioimmun-Assay (RIA) ermit-telt. In einigen Seren mit relativ hohen immunologischen LH-Aktivitaten waren die biologischen LH-Aktivitäten niedriger als erwartet. Demgegenüber konnten bei einigen Proben überdurchschnittlich hohe Werte für biologisch aktives LH nachgewiesen werden, obwohl diese Seren bei RIA normale LH-Werte aufwiesen. Eine andauernde Exposition der Gonaden solch hoher Mengen an biologisch aktivem LH, die durch RIA nicht aufgedeckt werden, kdnnte eine Gonaden-Insensitivität gegenüber diesem Hormon und damit Infertilität verursachen. Die Erfassung solcher Fälle mittels Radiorezeptor-Assay könnte die Therapie dieser Individuen ermöglichen bzw. sie von der Therapie ausschließen.
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