Aim: A preceding exploratory analysis has shown that follicle-stimulating hormone (FSH) was significantly correlated to and predicted by prostate-specific antigen (PSA) in a prostate cancer population. The aim of the study was to evaluate FSH physiopathology along the pituitary-testicular-prostate (PTP) axis at the time of initial diagnosis of prostate cancer in an operated population clustered according to the FSH/PSA ratio. Patients and Methods: The study included 93 patients who underwent standard radical prostatectomy. Age, percentages of positive cores at transrectal ultrasound scan biopsy (TRUSB) (P+), biopsy Gleason score (bGS), pathology Gleason score (pGS), luteinizing hormone (LH), FSH, prolactin hormone (PRL), total testosterone (TT), free testosterone (FT), estradiol (ESR) and PSA were the continuous variables. Category variables were pT and biopsy/pathology Gleason pattern I/II (b/pGPI/II). The population was clustered according to the FSH/PSA ratio which was computed from empirical data and then ranked for clustering the population as groups A (range 0.13 ≤ FSH/PSA ≤ 0.20), B (range 0.20 < FSH/PSA ≤ 0.50), C (range 0.50 < FSH/PSA ≤ 0.75), D (range 0.75 < FSH/PSA ≤ 1.00), E (range 1.00 < FSH/PSA ≤ 1.25), F (range 1.25 < FSH/PSA ≤ 2.00), G (range 2.00 < FSH/PSA ≤ 2.25), H (range 2.25 < FSH/PSA ≤ 6.40) and I (range 6.40 < FSH/ PSA ≤ 19.40). The model was assessed by simple linear regression analysis and differences between the groups were investigated by analysis of variance (ANOVA) for continuous variables and by contingency tables for category variables. Results: FSH was significantly correlated to and predicted by PSA in groups A (p = 0.04), B (p < 0.0001), C (p < 0.0001), D (p < 0.0001), E (p < 0.0001), F (p < 0.0001), G (p < 0.0001), H (p = 0.0001) and I (p = 0.001). Also, clusters (A–I) differed significantly for mean values of FSH (p < 0.0001), LH (p < 0.0001), TT (p = 0.04), PSA (p < 0.0001), bGS (p = 0.005), pGS (p = 0.01) and PSA/FT ratio (p < 0.0001); moreover, the nine groups showed significant different frequency distributions of pGPI (p = 0.02), pGPII (p = 0.0002) and bGPI (p = 0.04). Conclusion: The ranking FSH/PSA ratio significantly clustered, along the PTP axis, an operated population diagnosed with prostate cancer. Also, the ranking FSH/PSA ratio selected prostate cancer clusters expressing different levels of hormonal disorder along the PTP axis and prognostic potential with different risks of progression. As a theory, in the current advancing world, the ranking FSH/PSA model might be considered as an interesting and effective tool for prostate cancer study as well as individualized, risk-adapted approaches of the disease. However, confirmatory studies are needed.

1.
Walsh PC: Chemoprevention in prostate cancer. N Engl J Med 2010;362:1237–1238.
2.
Huggins C, Hodges CV: Studies on prostate cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941;1:293–297.
3.
Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E: Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987;317:909–916.
4.
Stenman UH, Abrahamsson PA, Aus G, Lilja H, Bangma C, Hamdy FC, Boccon-Gibod L, Ekman P: Prognostic value of serum markers for prostate cancer. Scand J Urol Nephrol Suppl 2005;216:64–81.
5.
Monda JM, Myers RP, Bostwick DG, Oesterling JE: The correlation between serum prostate-specific antigen and prostate cancer is not influenced by the serum testosterone concentration. Urology 1995;46:62–64.
6.
Imamoto T, Suzuki H, Fukasawa S, Shimbo M, Inahara M, Komiya A, Ueda T, Shiraishi T, Ichikawa T: Pretreatment serum testosterone level as a predictive factor of pathological stage in localized prostate cancer patients treated with radical prostatectomy. Eur Urol 2005;47:308–312.
7.
Mearini L, Costantini E, Zucchi A, Mearini E, Bini V, Cottini E, Porena M: Testosterone levels in benign prostatic hypertrophy and prostate cancer. Urol Int 2008;80:134–140.
8.
Yano M, Imamoto T, Suzuki H, Fukasawa S, Kojima S, Komiya A, Naya Y, Ichikawa T: The clinical potential of pretreatment serum testosterone level to improve the efficiency of prostate cancer screening. Eur Urol 2007;51:375–380.
9.
Ide H, Yasuda M, Nishio K, Saito K, Isotani S, Kamiyama Y, Muto S, Horie S: Development of a nomogram for predicting high-grade prostate cancer on biopsy: the significance of serum testosterone levels. Anticancer Res 2008;28:2487–2492.
10.
Miller LR, Partin AW, Chan DW, Bruzek DJ, Dobs AS, Epstein JI, Walsh PC: Influence of radical prostatectomy on serum hormone levels. J Urol 1998;160:449–453.
11.
Olsson M, Ekstrom L, Schulze J, Kjellman A, Akre O, Rane A, Gustafsson O: Radical prostatectomy: influence on serum and urinary androgen levels. Prostate 2010;70:200–205.
12.
Harper ME, Pierrepoint CG, Griffiths K: Carcinoma of the prostate: relationship of pretreatment hormone levels to survival. Eur J Cancer Clin Oncol 1984;20:477–482.
13.
Chen SS, Chen KK, Lin AT, Chang YH, Wu HH, Chang LS: The correlation between pretreatment serum hormone levels and treatment outcome for patients with prostatic cancer and bony metastasis. BJU Int 2002; 89:710–713.
14.
Tao YX, Bao S, Ackermann DM, Lei ZM, Rao CV: Expression of luteinizing hormone/human chorionic gonadotropin receptor gene in benign prostatic hyperplasia and in prostate carcinoma in humans. Biol Reprod 1997;56:67–72.
15.
Dirnhofer S, Berger C, Hermann M, Steiner G, Madersbacher S, Berger P: Coexpression of gonadotropic hormones and their corresponding FSH-LH and LH/CG-receptors in the human prostate. Prostate 1998;35:212–220.
16.
Ben-Josef E, Yang SY, JI TH, Bidart JM, Garde SV, Chopra DP, Porter AT, Tang DG: Hormone-refractory prostate cancer cell express functional follicle-stimulating hormone receptor (FSHR). J Urol 1999;161:970–976.
17.
Mariani S, Salvatori L, Basciani S, Arizzi M, Franco G, Petrangeli E, Spera G, Gnessi L: Expression and cellular localization of follicle-stimulating hormone receptor in normal human prostate, benign prostatic hyperplasia and prostate cancer. J Urol 2006;175:2072–2077.
18.
Radu A, Pichon C, Camparo P, Antoine M, Allory Y, Couvelard A, Fromont G, Hai MT, Ghinea N: Expression of follicle-stimulating hormone receptor in tumor blood vessels. N Engl J Med 2010;363:1621–1630.
19.
Huhtaniemi: Are gonadotropins tumorigenic – a critical review of clinical and experimental data. Mol Cell Endocrinol 2010;329:56–61.
20.
Hammond GL, Kontturi M, Maattala P, Puukka M, Vihko R: Serum FSH, LH and prolactin in normal males and patients with prostatic diseases. Clin Endocrinol 1977;7:129–135.
21.
Kumar VL, Wafhwa SN, Kumar V, Farooq A: Androgen, estrogen, and progesterone receptor contents and serum hormone profiles in patients with benign hypertrophy and carcinoma of the prostate. J Surg Oncol 1990;44:122–128.
22.
Anderson SO, Adami HO, Bergstrom R, Wide B: Serum pituitary and sex steroid hormone levels in the etiology of prostatic cancer: a population-based case control study. Br J Cancer 1993;68:97–102.
23.
Schatzl G, Madersbacher S, Thurridl T, Waldmuller J, Kramer G, Haitel A, Marberger M: High-grade prostate cancer is associated with low serum testosterone levels. Prostate 2001;47:52–58.
24.
Hilz H, Graefen M, Noldus J, Hammerer P, Knabbe C, Huland E, Huland H: Advanced prostate cancer is associated with a decrease in serum luteinizing hormone. Eur Urol 2000;38:243–249.
25.
Madersbacher S, Shatzl G, Bieglmayer C, Reiter BW, Gassner C, Berger P, Zidek T, Marberger M: Impact of radical prostatectomy and TURP on the hypothalamic-pituitary-gonadal axis. Urology 2002;60:869–874.
26.
Sofikerim M, Eskicorapaci S, Oruc O, Ozen H: Hormonal predictors of prostate cancer. Urol Int 2007;79:913–918.
27.
Imamoto T, Suzuki H, Yano M, Kawamura K, Kamiya N, Araki K, Komiya A, Naya Y, Shiraishi T, Ichikawa T: Does the presence of prostate cancer affect serum testosterone levels in clinically localized prostate cancer patients? Prostate Cancer Prostatic Dis 2009;12:78–82.
28.
Fodstad P, Bjoro T, Torlakovic G, Fossa SD: No association of serum gonadal or pituitary hormone with prognostic parameters in stages T1 to T3 pN0M0 prostate cancer. J Urol 2002;168:1188–1192.
29.
Porcaro AB, Migliorini F, Petrozziello A, Sava T, Romano M, Caruso B, Cocco C, Ghimenton C, Zecchini Antoniolli S, Lacola V, Rubilotta E, Monaco C, Comunale L: Investigative clinical study on prostate cancer. VI. Follicle stimulating hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population. Urol Int 2012;88:150–157.
30.
Flemming ID, Cooper JS, Henson DE, Hutte RVP, Kennedy BJ, Murphy GP, O’Sullivan B, Sobin LH, Yarbro JN (eds): American Joint Committee on Cancer Staging Manual, ed 5. Philadelphia, Lippincott, 1997, pp 219–222.
31.
Porter AT, Ben-Josef E: Humoral mechanisms in prostate cancer: a role for FSH. Urol Oncol 2001;6:131–138.
32.
Porcaro AB, Migliorini F, Petrozziello A, Antoniolli SZ, Rubilotta E, Lacola V, Sava T, Ghimenton C, Caruso B, Monaco C, Comunale L: Investigative clinical study on prostate cancer: on the role of the pretreatment total PSA to free testosterone ratio in selecting different biology groups of prostate cancer patients. Int Urol Nephrol 2009;42:673–681.
33.
Porcaro AB, Monaco C, Romano M, Petrozziello A, Rubilotta E, Lacola V, Sava T, Ghimenton C, Caruso B, Antoniolli SZ, Migliorini F, Comunale L: Investigative clinical study on prostate cancer. II. On the role of the pretreatment total PSA to free testosterone ratio as a marker assessing prostate cancer prognostic groups after radical retropubic prostatectomy. Urol Int 2010;85:152–158.
34.
Porcaro AB, Petrozziello A, Romano M, Sava T, Ghimenton C, Caruso B, Migliorini F, Zecchini Antoniolli S, Rubilotta E, Lacola V, Monaco C, Comunale L: Investigative clinical study on prostate cancer. III. Exploring total PSA and free testosterone distributions and linear correlations in groups and subgroups of operated prostate cancer patients according to the total PSA/FT ratio. Urol Int 2010;85:407–409.
35.
Porcaro AB, Petrozziello A, Migliorini F, Caruso B, Cocco C, Sava T, Ghimenton C, Romano M, Monaco C, Comunale L: Investigative clinical study on prostate cancer. V. Luteinizing hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population. Anticancer Res 2011;31:1071–1078.
36.
Porcaro AB, Ghimenton C, Petrozziello A, Migliorini F, Romano M, Sava T, Caruso B, Cocco C, Zecchini Antoniolli S, Lacola V, Rubilotta E, Monaco C, Comunale L: Investigative clinical study on prostate cancer. VII. Prolactin and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population. Anticancer Res 2011;31:3913–3920.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.