Inhibin B

CPT: 83520
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Special Instructions

This test may exhibit interference when sample is collected from a person who is consuming a supplement with a high dose of biotin (also termed as vitamin B7 or B8, vitamin H, or coenzyme R). It is recommended to ask all patients who may be indicated for this test about biotin supplementation. Patients should be cautioned to stop biotin consumption at least 72 hours prior to the collection of a sample.


Expected Turnaround Time

3 - 7 days



Related Documents


Specimen Requirements


Specimen

Serum


Volume

0.6 mL


Minimum Volume

0.3 mL (Note: This volume does not allow for repeat testing.)


Container

Red-top tube or gel-barrier tube


Collection

If red-top tube is used, transfer separated serum to a plastic transport tube.


Storage Instructions

Room temperature


Stability Requirements

Temperature

Period

Room temperature

7 days

Refrigerated

21 days

Frozen

21 days

Freeze/thaw cycles

Stable x3


Causes for Rejection

Nonserum sample received


Test Details


Use

This test is used to assess the function of the antral follicles of the ovaries in women or the Sertoli cells of the testes in men. It serves as an adjunct to follicle-stimulating hormone testing during infertility evaluation.

This test can aid in the diagnosis of granulosa cell tumors and mucinous epithelial ovarian tumors and helps with monitoring of patients with granulosa cell tumors and epithelial mucinous-type tumors of the ovary known to over-express inhibin B.


Limitations

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

Values obtained with different assay methods or kits cannot be used interchangeably.

Inhibin values fluctuate during the menstrual cycle. Inhibin levels in premenopausal women should be interpreted with caution.

Do not interpret serum inhibin levels as absolute evidence of the presence or the absence of malignant disease. Use results in conjunction with information from the clinical evaluation of the patient and other diagnostic procedures.

The majority of studies for inhibin B as ovarian cancer markers have been limited to postmenopausal women where the levels of inhibin are normally very low. Inhibin levels vary in relation to the menstrual cycle and, therefore, are difficult to interpret in premenopausal women.


Methodology

AnshLite™ Enzyme Linked Immunoassay


Reference Interval

See table.

Inhibin B

Male

(Age)

Range

(pg/mL)

Female

(Age)

Range

(pg/mL)

<12 m

68.0−630.0

<6 y

<73.0

12 to 23 m

87.0−419.0

6 to 9 y

<129.0

2 to 5 y

42.0−268.0

10 y

<103.0

6 to 9 y

35.0−167.0

11 y

20.0−186.0

10 y

50.0−310.0

12 to 18 y

<362.0

11 y

104.0−481.0

Early follicular

<261.0

12 to 17 y

74.0−470.0

Late follicular

<286.0

18 to 49 y

66.9−300.0

Periovulatory

<189.0

>49 y

34.9−289.2

Midluteal

<164.0

End luteal

<107.0

Postmenopausal

<17.0

Inhibin B performed by AnshLite™ Enzyme Linked Immunoassay methodology.

Values obtained with different assay methods or kits cannot be used interchangeably.


Additional Information

Historically, inhibin was the name given to a component of serum that was found to inhibit secretion of follicle-stimulating hormone (FSH) by the pituitary.1,2 In recent years, a number of inhibin proteins have been characterized and specific immunoassays have been developed for both inhibin A and inhibin B.1,3 These hormones are members of the transforming growth factor-B super family.2 In women, inhibin B is produced primarily by small developing antral follicles of the ovaries.1 The Sertoli cells of the testes are the primary source of this hormone in men.1,4

In young girls, the concentrations of inhibin B increase as puberty progresses.5-7 Therefore, its measurement could aid in determining gonadal maturity and diagnosing precocious puberty in girls.5,7,8 Inhibin B has been used to distinguish between congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) in girls.9,10 Once women reach reproductive age, inhibin B levels change with the menstrual cycle.5 inhibin B is thought to play an important role in the regulation of FSH levels during the early and midfollicular phase.1 Levels are maximal in the midfollicular phase with a spike at ovulation before falling to basal levels in the luteal phase. In postmenopausal women, inhibin B levels fall to <5 pg/mL.11

A woman's fertility declines with age, in large part, due to a drop in the number of follicles in the ovary, also referred to as diminished ovarian reserve. It has been suggested that the measurement of inhibin B, used in conjunction with other evaluating criteria, can be useful in evaluating the status of ovarian reserve.12,13 This assessment can be of value in estimating the probability of successful retrieval of oocytes through assisted reproductive technologies or in assessing the potential for natural pregnancy as a woman ages.1,12,14 In the early perimenopausal phase of the menopausal transition, the circulating follicular phase levels of inhibin B decline before changes in estradiol or inhibin A are observed.12,14-16 Follicular phase inhibin B measurement may be useful for predicting the onset of menopause.

During the in vitro fertilization treatment, it is important to choose the correct level of ovarian stimulation. Insufficient stimulation can lead to a cancelled cycle due to a poor response,15,17-19 and too much stimulation can run the risk of ovarian hyperstimulation syndrome (OHSS). Inhibin B measurement has been used as an aid in determining OHSS cycles and in managing this dangerous condition.

Granulosa cell tumor of the ovary (GCT) is a rare ovarian tumor with nonspecific symptoms.20,21 In these patients, high levels of inhibin B produced by the granulosa cells lead to low levels of FSH and secondary amenorrhea, causing infertility. In premenopausal women, irregular menses or secondary amenorrhea may be an early symptom of GCT and, in postmenopausal women, the most common manifestation is vaginal bleeding. Additionally, endometrial abnormalities can be associated due to estrogenic secretion. Therefore, inhibin B level can differentiate GCT from other causes of secondary amenorrhea. Elevations of serum inhibin B are detected in the majority of patients with granulosa cell tumors.22-27 The frequency of elevated levels varies amongst studies, likely due to the different assays used. In GCT patients, inhibin B is superior to inhibin A, with reported sensitivities between 88-100% for inhibin B, and 67-77% for inhibin A, respectively.25 Anti-Mullerian Hormone (AMH) has also been validated as a marker for GCT, and both AMH and inhibin B are equally sensitive (92 and 93%) and specific (82 and 83%) in this disease.28 In addition, both markers are also elevated in relapsed disease and their levels positively correlate with disease burden.28 The combination of AMH and inhibin B seems to be superior to inhibin B alone in detecting macroscopic disease. AMH and inhibin B levels have been reported to rise several months or even years before the onset of clinical symptoms of the relapse, the lead-times have been reported 0.9–2.8 years for inhibin B, and 3.4 years for AMH.25,28 Inhibin B also appears to be a suitable serum marker for epithelial tumors of the mucinous type with about 55% to 60% having elevated inhibin B levels.29

In males, inhibin B is produced by the Sertoli cells of the testes and serves as the primary regulator of FSH secretion detectable throughout life. Levels are relatively high in infant boys and decrease gradually to their lowest levels between 6 to 10 years of age.4,30,31 During childhood, the basal serum inhibin B levels have been used as a direct marker of the presence and function of testicular tissue and have been applied to the diagnosis of patients with cryptorchidism or ambiguous genitalia.30,32 Inhibin B has been used to distinguish between CHH and constitutional delay of growth and puberty CDGP in boys.9,10,33

Inhibin B can also be used as a direct marker of Sertoli cell function and spermatogenesis in adult males.1,4,30,34-38 Serum inhibin B levels have been shown to correlate with testicular volume and sperm density. Very low levels of inhibin B are found in men with no or negligible sperm production.39 A combined measurement of inhibin B and FSH has been shown to be a better indicator of spermatogenesis adequacy than either marker alone.40 Inhibin B concentration has also been shown to predictive for long-term azoospermia in men treated for testicular cancer.41


Footnotes

1. Groome NP, Evans LW. Does measurement of inhibin have a clinical role? Ann Clin Biochem. 2000 Jul;37(Pt 4):419-431.10902857
2. Risbridger GP, Schmitt JF, Robertson DM. Activins and inhibins in endocrine and other tumors. Endocr Rev. 2001 Dec;22(6):836-858.11739336
3. Makanji Y, Zhu J, Mishra R, et al. Inhibin at 90: from discovery to clinical application, a historical review. Endocr Rev. 2014 Oct;35(5):747-794.25051334
4. Winters SJ. Laboratory Assessment of Testicular Function. 2020 Feb 29. In: Feingold KR, Anawalt B, Boyce A, et al, eds. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. 2020 Feb 29.25905368
5. Sehested A, Juul AA, Andersson AM, et al. Serum inhibin A and inhibin B in healthy prepubertal, pubertal, and adolescent girls and adult women: Relation to age, stage of puberty, menstrual cycle, follicle-stimulating hormone, luteinizing hormone, and estradiol levels. J Clin Endocrinol Metab. 2000 Apr;85(4):1634-1640.10770209
6. Crofton PM, Evans AEM, Groome NP, Taylor MRH, Holland CV, Kelnar CJH. Dimeric inhibins in girls from birth to adulthood: Relationship with age, pubertal stage, FSH and oestradiol. Clin Endocrinol (Oxf). 2002 Feb;56(2):223-230.11874414
7. Tencer J, Lemaire P, Brailly-Tabard S, Brauner R. Serum inhibin B concentration as a predictor of age at first menstruation in girls with idiopathic central precocious puberty. PLoS One. 2018 Dec 14;13(12):e0205810.30550563
8. Binder G, Schweizer R, Haber P, Blumenstock G, Braun R. Accuracy of Endocrine Tests for Detecting Hypogonadotropic Hypogonadism in Girls. J Pediatr. 2015 Sep;167(3):674-678.e1.26095287
9. Gao Y, Du Q, Liu L, Liao Z. Serum inhibin B for differentiating between congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty: a systematic review and meta-analysis. Endocrine. 2021 Jun;72(3):633-643.33464540
10. Sukumar SP, Bhansali A, Sachdeva N, et al. Diagnostic utility of testosterone priming prior to dynamic tests to differentiate constitutional delay in puberty from isolated hypogonadotropic hypogonadism. Clin Endocrinol (Oxf). 2017 May;86(5):717-724.28261833
11. Burger HG, Hale GE, Robertson DM, Dennerstein L. A review of hormonal changes during the menopausal transition: focus on findings from the Melbourne Women's Midlife Health Project. Hum Reprod Update. 2007 Nov-Dec;13(6):559-565.17630397
12. Welt CK, McNicholl DJ, Taylor AE, Hall JE. Female reproductive aging is marked by decreased secretion of dimeric inhibin. J Clin Endocrinol Metab. 1999 Jan;84(1):105-111.9920069
13. Wen J, Huang K, Du X, et al. Can Inhibin B Reflect Ovarian Reserve of Healthy Reproductive Age Women Effectively? Front Endocrinol (Lausanne). 2021 Apr 14;12:626534.33935966
14. Burger HG, Cahir N, Robertson DM, et al. Serum inhibins A and B fall differentially as FSH rises in perimenopausal women. Clin Endocrinol (Oxf). 1998 Jun;48(6):809-813. Erratum: 1998 Oct;49(4):550.9713572
15. Danforth DR, Arbogast LK, Mroueh J, et al. Dimeric inhibin: A direct marker of ovarian aging. Fertil Steril. 1998 Jul;70(1):119-123.9660432
16. Santoro N, Adel T, Skurnick JH. Decreased inhibin tone and increased activin A secretion characterize reproductive aging in Women. Fertil Steril. 1999 Apr;71(4):658-662.10202875
17. Seifer DB, Lambert-Messerlian G, Hogan JW, Gardiner AC, Blazar AS, Berk CA. Day 3 serum inhibin-B is predictive of assisted reproductive technologies outcome. Fertil Steril. 1997 Jan;67(1):110-114.8986693
18. Seifer DB, Scott RT Jr, Bergh PA, et al. Women with declining ovarian reserve may demonstrate a decrease in day 3 serum inhibin B before a rise in day 3 follicle-stimulating hormone. Fertil Steril. 1999 Jul;72(1):63-65.10428149
19. Fawzy M, Lambert A, Harrison RF, et al. Day 5 inhibin B levels in a treatment cycle are predictive of IVF outcome. Hum Reprod. 2002 Jun;17(6):1535-1543.12042274
20. Mancari R, Portuesi R, Colombo N. Adult granulosa cell tumours of the ovary. Curr Opin Oncol. 2014 Sep;26(5):536-541.25024052
21. Jamieson S, Fuller PJ. Molecular pathogenesis of granulosa cell tumors of the ovary. Endocr Rev. 2012 Feb;33(1):109-144.22240241
22. Gică C, Cigăran RG, Botezatu R, et al. Secondary Amenorrhea and Infertility Due to an Inhibin B Producing Granulosa Cell Tumor of the Ovary. A Rare Case Report and Literature Review. Medicina (Kaunas). 2021 Aug 17;57(8):829.34441035
23. Färkkilä A, Haltia UM, Tapper J, McConechy MK, Huntsman DG, Heikinheimo M. Pathogenesis and treatment of adult-type granulosa cell tumor of the ovary. Ann Med. 2017 Aug;49(5):435-447.28276867
24. Geerts I, Vergote I, Neven P, Billen J. The role of inhibins B and antimüllerian hormone for diagnosis and follow-up of granulosa cell tumors. Int J Gynecol Cancer. 2009 Jul;19(5):847-855.19574772
25. Mom CH, Engelen MJA, Willemse PHB, et al. Granulosa cell tumors of the ovary: the clinical value of serum inhibin A and B levels in a large single center cohort. Gynecol Oncol. 2007 May;105(2):365-372.17306349
26. Robertson DM, Cahir N, Burger HG, Mamers P, Groome N. Inhibin forms in serum from postmenopausal women with ovarian cancers. Clin Endocrinol (Oxf). 1999 Mar;50(3):381-386.10435065
27. Petraglia F, Luisi S, Pautier P, et al. Inhibin B is the major form of inhibin/activin family secreted by granulosa cell tumors. J Clin Endocrinol Metab. 1998 Mar;83(3):1029-1032.9506769
28. Färkkilä A, Koskela S, Bryk S, et al. The clinical utility of serum anti-Müllerian hormone in the follow-up of ovarian adult-type granulosa cell tumors--A comparative study with inhibin B. Int J Cancer. 2015 Oct 1;137(7):1661-1671.25808251
29. Walentowicz P, Krintus M, Sadlecki P, et al. Serum inhibin A and inhibin B levels in epithelial ovarian cancer patients. PLoS One. 2014 Mar 5;9(3):e90575.24599287
30. Andersson AM. Inhibin B in the assessment of seminiferous tubular function. Baillieres Best Pract Res Clin Endocrinol Metab. 2000 Sep;14(3):389-397.11517906
31. Crofton PM, Evans AEM, Groome NP, Taylor MRH, Holland CV, Kelnar CJH. Inhibin B in boys from birth to adulthood: Relationship with age, pubertal stage, FSH, and testosterone. Clin Endocrinol (Oxf). 2002 Feb;56(2):215-221.11874413
32. Esposito S, Cofini M, Rigante D, et al. Inhibin B in healthy and cryptorchid boys. Ital J Pediatr. 2018 Jul 16;44(1):81.30012176
33. Rohayem J, Nieschlag E, Kliesch S, Zitzmann M. Inhibin B, AMH, but not INSL3, IGF1 or DHEAS support differentiation between constitutional delay of growth and puberty and hypogonadotropic hypogonadism. Andrology. 2015 Sep;3(5):882-887.26266675
34. Anawalt BD, Bebb RA, Matsumoto AM, et al. Serum inhibin B levels reflect Sertoli cell function in normal men and men with testicular dysfunction. J ClinEndocrinol Metab. 1996 Sep;81(9):3341-3345.8784094
35. Klingmüller D, Haidl G. Inhibin B in men with normal and disturbed spermatogenesis. Hum Reprod. 1997 Nov;12(11):2376-2378.9436667
36. Barbotin AL, Ballot C, Sigala J, et al. The serum inhibin B concentration and reference ranges in normozoospermia. Eur J Endocrinol. 2015 Jun;172(6):669-676.25740852
37. Andersson AM, Juul A, Petersen JH, Müller J, Groome NP, Skakkebaek NE. Serum inhibin B in healthy pubertal and adolescent boys: relation to age, stage of puberty, and follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol levels. J ClinEndocrinol Metab. 1997 Dec;82(12):3976-3981.9398699
38. Hipler UC, Hochheim B, Knöll B, Tittelbach J, Schreiber G. Serum inhibin B as a marker for spermatogenesis. Arch Androl. 2001 May-Jun;46(3):217-222.11339648
39. Pierik FH, Vreeburg JT, Stijnen T, De Jong FH, Weber RF. Serum inhibin B as a marker of spermatogenesis. J Clin Endocrinol Metab. 1998 Sep;83(9):3110-3114.9745412
40. von Eckardstein S, Simoni M, Bergmann M, et al. Serum inhibin B in combination with serum follicle-stimulating hormone (FSH) is a more sensitive marker than serum FSH alone for impaired spermatogenesis in men, but cannot predict the presence of sperm in testicular tissue samples. J Clin Endocrinol Metab. 1999 Jul;84(7):2496-2501.10404826
41. Isaksson S, Eberhard J, Ståhl O, et al. Andrology. 2014 Mar;2(2):252-258.24519955

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
146795 Inhibin B 34319-4 146796 Inhibin B pg/mL 34319-4

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