Inhibin B: are modified ranges needed for orchiectomised testicular cancer patients?

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Abstract

Inhibin B is a gonadal hormone that downregulates the pituitary production of follicle-stimulating hormone (FSH). In recent years, inhibin B has proved to be an excellent marker of spermatogenesis and even a predictive factor for the recovery of fertility in patients undergoing orchiectomy and antineoplastic treatments. We propose to study inhibin B levels in orchiectomised testicular cancer patients, in order to identify a minimum value representative of normal semen quality. This retrospective study evaluates hormonal and semen parameters of 290 normozoospermic patients attending the Laboratory of Seminology - Sperm Bank “Loredana Gandini” (Rome, Italy) for cryopreservation of seminal fluid following a diagnosis of testicular cancer (TC group) and 117 healthy, normozoospermic men as a control group (CTR group). The percentile distribution of gonadotropin and inhibin B values in the TC and CTR groups was analyzed. There was a statistically significant difference between the two groups in the levels of all hormones ( P ≤ 0.001) and in all semen parameters ( P < 0.05). About 20% of TC patients revealed inhibin B levels below the 5 ^th percentile of CTR group, despite normozoospermia, and 31.4% had normal spermatogenesis in the presence of FSH values >95 ^th percentile of CTR group. Orchiectomised patients for testicular cancer presented inhibin B levels lower than healthy patients, despite normozoospermia. Our study revealed the poor sensitivity of the current inhibin B reference range when applied to monorchidic patients, suggesting the need to establish more representative ranges to enable more appropriate counseling in relation to the patient's new endocrine condition.

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Most cited references 25

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The World Health Organization 2016 classification of testicular germ cell tumours: a review and update from the International Society of Urological Pathology Testis Consultation Panel.

Sean R. Williamson, Brett Delahunt, Cristina Magi-Galluzzi … (2017)

Since the last World Health Organization (WHO) classification scheme for tumours of the urinary tract and male genital organs, there have been a number of advances in the understanding, classification, immunohistochemistry and genetics of testicular germ cell tumours. The updated 2016 draft classification was discussed at an International Society of Urological Pathology Consultation on Testicular and Penile Cancer. This review addresses the main updates to germ cell tumour classification. Major changes include a pathogenetically derived classification using germ cell neoplasia in situ (GCNIS) as a new name for the precursor lesion, and the distinction of prepubertal tumours (non-GCNIS-derived) from postpubertal-type tumours (GCNIS-derived), acknowledging the existence of rare benign prepubertal-type teratomas in the postpubertal testis. Spermatocytic tumour is adopted as a replacement for spermatocytic seminoma, to avoid potential confusion with the unrelated usual seminoma. The spectrum of trophoblastic tumours arising in the setting of testicular germ cell tumour continues to expand, to include epithelioid and placental site trophoblastic tumours analogous to those of the gynaecological tract. Currently, reporting of anaplasia (seminoma or spermatocytic tumour) or immaturity (teratoma) is not required, as these do not have demonstrable prognostic importance. In contrast, overgrowth of a teratomatous component (somatic-type malignancy) and sarcomatous change in spermatocytic tumour indicate more aggressive behaviour, and should be reported.

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Reproductive hormone reference intervals for healthy fertile young men: evaluation of automated platform assays.

R Kazlauskas, Carol Holden, David Handelsman … (2005)

Management of male infertility and/or androgen deficiency requires accurate hormonal measurements with valid reference intervals. The objective of this study was to develop a valid reference panel of blood samples from healthy eugonadal young men with verified normal reproductive function and to use this panel to evaluate the performance of seven fully automated, commercial multiplex immunoassay platforms used to measure serum total testosterone (T), LH, and FSH. This was an observational study of consistency among seven different automated immunoassays for each of total T, LH, and FSH. Each method was implemented in two laboratories, with each repeating the analysis of the full reference panel samples twice. Serum T concentrations were also measured by gas chromatography/mass spectrometry (GC/MS), and serum inhibin B levels were determined by an ELISA. The study was performed at commercial, high-volume, clinical pathology laboratories. From 147 men screened, sera from 124 healthy, reproductively normal men (age, 21-35 yr) with normal sperm output were used as a reference panel. All laboratories selected for elite performance in the national immunoassay quality assurance program agreed to participate. For each of the 868 assays, descriptive statistics were calculated in the natural and log-transformed scales and were analyzed by nested, repeated measures ANOVA after log transformation. Reference intervals, defined as 95% confidence limits, were calculated using arithmetic (natural scale), geometric (log scale) and nonparametric methods. Descriptive statistics and reference intervals for serum T, LH, and FSH differed widely and significantly between methods, but variation between laboratories for the same assay was negligible. All T methods showed significant differences in regression slope and intercept in deviance plots as well as in estimated reference ranges compared with the independent GC/MS reference method. Although similar between-method differences existed for gonadotropin assays, the smaller quantitative discrepancies allowed assignment of consensus reference intervals for serum FSH (1.3-8.4 IU/liter) and LH (1.6-8.0 IU/liter), although these differed from manufacturers' currently quoted expected values. Using a reference panel of sera from healthy eugonadal young men with verified normal reproductive function, major differences exist between commercial T immunoassays as well as divergence from the GC/MS standard. This impairs their clinical diagnostic utility and requires substantial improvements in automated T immunoassay technologies or a switch to GC/MS methods. Gonadotropin assays showed less variability, but current high-throughput immunoassays remain suboptimal to confirm accurate diagnosis of azoospermia or androgen deficiency.

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Inhibin B in male reproduction: pathophysiology and clinical relevance.

Jane Simoni, E Nieschlag, Sarah Meachem (2001)

The recent availability of specific inhibin assays has demonstrated that inhibin B is the relevant circulating inhibin form in the human male. Inhibin B is a dimer of an alpha and a betaB subunit. It is produced exclusively by the testis, predominantly by the Sertoli cells in the prepubertal testis, while the site of production in the adult is still controversial. Inhibin B controls FSH secretion via a negative feedback mechanism. In the adult, inhibin B production depends both on FSH and on spermatogenic status, but it is not known in which way germ cells contribute to inhibin B production. The regulation of inhibin B production changes during life. There is an inhibin B peak in serum shortly after birth only partly correlated with an increase in serum FSH, probably reflecting the proliferating activity of the Sertoli cells during this phase of life. Afterwards, inhibin B levels decrease and remain low until puberty, when they rise again, first as a consequence of FSH stimulation and then as a result of the combined regulation by FSH and the ongoing spermatogenesis. In the adult, serum inhibin B shows a clear diurnal variation closely related to that of testosterone. The administration of FSH increases the secretion of inhibin B in normal men, but is much more pronounced in males with secondary hypogonadism. The treatment of infertile men with FSH, however, does not result in an unequivocal inhibin B increase. There is a clear inverse relationship between serum inhibin B and FSH in the adult. Serum inhibin B levels are strongly positively correlated with testicular volume and sperm counts. In infertile patients, inhibin B decreases and FSH increases. In general, there is very good correlation with the degree of spermatogenetic damage, with the arrest at the earlier stages having the lowest inhibin B levels. However, for unknown reasons, there are cases of Sertoli-cell-only syndrome with normal inhibin B levels. Inhibin B and FSH together are a more sensitive and specific marker for spermatogenesis than either one alone. However, the inhibin B concentrations are not a reliable predictor of the presence of sperm in biopsy samples for testicular sperm extraction. Suppression of spermatogenesis with testosterone and gestagens leads to a partial reduction of inhibin B in serum but it is never completely suppressed. In contrast, testicular irradiation in monkeys or humans leads to a rapid and dramatic decrease of inhibin B, which becomes undetectable when germ cells are completely absent. In summary, although inhibin B is a valuable index of spermatogenesis, the measurement of serum inhibin B levels is still of limited clinical relevance for individual patients.

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Author and article information

Journal

Journal ID (nlm-ta): Asian J Androl

Journal ID (iso-abbrev): Asian J. Androl

Journal ID (publisher-id): AJA

Title: Asian Journal of Andrology

Publisher: Wolters Kluwer - Medknow (India )

ISSN (Print): 1008-682X

ISSN (Electronic): 1745-7262

Publication date (Print): Jul-Aug 2019

Publication date (Electronic): 07 December 2018

Volume: 21

Issue: 4

Pages: 332-336

Affiliations

[1 ]Laboratory of Seminology, Sperm Bank “Loredana Gandini”, Department of Experimental Medicine, Medical Pathophysiology Section, “Sapienza” University of Rome, Rome 00161, Italy

[2 ]Hormone Laboratory, Department of Experimental Medicine, Medical Pathophysiology Section, “Sapienza” University of Rome, Rome 00161, Italy

Author notes

Correspondence: Dr. F Lombardo ( francesco.lombardo@ 123456uniroma1.it )

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Publisher ID: AJA-21-332

DOI: 10.4103/aja.aja_93_18

PMC ID: 6628744

PubMed ID: 30531061

SO-VID: 35fbc25e-b6d5-492f-94fb-a70eb158a8a1

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Inhibin B: are modified ranges needed for orchiectomised testicular cancer patients?

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Cancer Metabolism

Most cited references 25

The World Health Organization 2016 classification of testicular germ cell tumours: a review and update from the International Society of Urological Pathology Testis Consultation Panel.

Reproductive hormone reference intervals for healthy fertile young men: evaluation of automated platform assays.

Inhibin B in male reproduction: pathophysiology and clinical relevance.

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