Inhibin B

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 These hormones are members of the transforming growth factor-B super family.² Structurally, the inhibins consist of dimers of two dissimilar protein subunits. The α-subunit is common to both inhibins. The α-subunit of inhibin B is covalently linked to a β-B subunit by disulfide bridges. 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

In young girls, the concentrations of inhibin B increase as puberty progresses.^3,4 Therefore, its measurement could aid in determining gonadal maturity and diagnosing precocious puberty in girls.³ Once women reach reproductive age, inhibin B levels change with the menstrual cycle.³ 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.

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.⁵ 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.^1,5,6 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.^5-8 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,^7,9-11 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.

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.^12,13 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.¹² A traditional test for testicular function in prepubertal boys with testicular disorders is to measure the increase in testosterone after administration of human chorionic gonadotropin (hCG).¹⁴ Inhibin B levels have been shown to be correlated well with results of hCG stimulation tests.¹⁴

Inhibin B can also be used as a direct marker of Sertoli cell function and spermatogenesis in adult males.^1,12,15,16 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.¹⁷ A combined measurement of inhibin B and FSH has been shown to be a better indicator of spermatogenesis adequacy than either marker alone.¹⁸

1. Groome NP, Evans LW. Does measurement of inhibin have a clinical role? Ann Clin Biochem. 2000; 37(Pt4):419-431. PubMed 10902857

2. Risbridger GP, Schmitt JF, Robertson DM. Activins and inhibins in endocrine and other tumors. Endocr Rev. 2001; 22(6):836-858. PubMed 11739336

3. 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; 85(4):1634-1640. PubMed 10770209

4. Crofton PM, Evans AE, Groome NP, et al. Dimeric inhibins in girls from birth to adulthood: Relationship with age, pubertal stage, FSH and oestradiol. Clin Endocrinol (Oxf). 2002; 56(2):223-230. PubMed 11874414

5. Welt CK, McNicholl DJ, Taylor AE, et al. Female reproductive aging is marked by decreased secretion of dimeric inhibin. J Clin Endocrinol Metab. 1999; 84(1):105-111. PubMed 9920069

6. 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; 48(6):809-813. Erratum: 1998; 49(4):550. PubMed 9713572

7. Danforth DR, Arbogast LK, Mroueh J, et al. Dimeric inhibin: A direct marker of ovarian aging. Fertil Steril. 1998; 70(1):119-123. PubMed 9660432

8. Santoro N, Adel T, Skurnick JH. Decreased inhibin tone and increased activin A secretion characterize reproductive aging in Women. Fertil Steril. 1999; 71(4):658-662. PubMed 10202875

9. Seifer DB, Lambert-Messerlian G, Hogan JW, et al. Day 3 serum inhibin-B is predictive of assisted reproductive technologies outcome. Fertil Steril. 1997; 67(1):110-114. PubMed 8986693

10. 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; 72(1):63-65. PubMed 10428149

11. 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; 17(6):1535-1543. PubMed 12042274

12. Andersson AM. Inhibin B in the assessment of seminiferous tubular function. Baillieres Best Pract Res Clin Endocrinol Metab. 2000; 14(3):389-397. PubMed 11517906

13. Crofton PM, Evans AE, Groome NP, et al. Inhibin B in boys from birth to adulthood: Relationship with age, pubertal stage, FSH, and testosterone. Clin Endocrinol (Oxf). 2002; 56(2):215-221. PubMed 11874413

14. Kubini K, Zachmann M, Albers N, et al. Basal inhibin B and the testosterone response to human chorionic gonadotropin correlate in prepubertal boys. J Clin Endocrinol Metab. 2000; 85(1):134-138. PubMed 10634376

15. Anawalt BD, Bebb RA, Matsumoto AM, et al. Serum inhibin B levels reflect Sertoli cell function in normal men and men with testicular dysfunction. 1996; 81(9):3341-3345. PubMed 8784094

16. Klingmuller D, Haidl G. Inhibin B in men with normal and disturbed spermatogenesis. Hum Reprod. 1997; 12(11):2376-2378. PubMed 9436667

17. Pierik FH, Vreeburg JT, Stijnen T, et al. Serum inhibin B as a marker of spermatogenesis. J Clin Endocrinol Metab. 1998; 83(9):3110-3114. PubMed 9745412

18. von Eckardstein S, Simoni M, Bergmann M, et al. Serum inhibin B in combination with serum follicle-stimulatin