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.
Biochemical assessment of gonadal function during maturation in girls and in adult women can be troublesome. With the recent advent of specific assays for the gonadal peptides inhibin A and inhibin B, it might be possible to achieve a clearer picture of events. We therefore determined serum levels of inhibin A, inhibin B, FSH, LH and estradiol in a cross-sectional study of 403 healthy schoolgirls (aged 6 -20 yr) in relation to age and stage of puberty and in 181 healthy nonpregnant women (aged 20-32 yr) in relation to stage of the menstrual cycle. In addition, inhibin A and inhibin B were measured daily throughout the menstrual cycle in 10 healthy adult women. Levels of inhibin B are low or undetectable in prepubertal girls (median, 26.5 pg/mL; 95% prediction interval, <20-100 pg/mL), increase sharply through pubertal stage II to peak in stage III (median, 84 pg/mL; 95% prediction interval, 28-227 pg/mL) and thereafter decline through pubertal stages IV and V. These changes presumably reflect increasing ovarian stimulation through early puberty, resulting in an increased number of developing follicles, follicles reaching a later stage of development before undergoing atresia, or both. Declining levels in late puberty and adulthood probably reflect the onset of the menstrual cycle and the subsequent appearance of the luteal phase, where inhibin B levels are low. Inhibin A levels are undetectable or very low in early puberty (median, <7 pg/mL; 95% prediction interval, <7-14) pg/mL), increasing gradually through pubertal stages to reach their highest values in adult women (median, 21.5 pg/mL; 95% prediction interval, <7-129 pg/mL). Levels of inhibin A greater than 19 pg/mL are only seen in postmenarcheal girls in puberty and in adult women, again consistent with inhibin A being primarily produced by the corpus luteum. Determining cut-off levels of serum inhibin B regarding whether a girl had entered puberty resulted in similar (low) sensitivities and specificities as those found for cut-off levels of LH or estradiol due to the large overlap between serum values in Tanner stages I and II. Correlations between inhibin A and inhibin B and FSH, LH, and estradiol within pubertal stages are presented. In early puberty both inhibin A and inhibin B correlated positively with LH and FSH. In late puberty inhibin A correlated negatively with FSH and did not correlate with LH; inhibin B still correlated positively with both FSH and LH, now most strongly with FSH. In adult women during the menstrual cycle, serum inhibin B levels increased during the follicular phase, indicating the greatest production by follicles in early stages of development. In contrast, serum inhibin A levels peaked during the luteal phase, indicating the greatest production by the corpus luteum. In conclusion, serum inhibin A and inhibin B levels in normal puberty in girls show consistency with our knowledge of the manner in which these hormones are secreted within the menstrual cycle in adult women. The presented reference values may be of use in the clinical evaluation of pubertal development in girls.
Sehested
A
A
Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark. sehested@rh.dk
Juul
A A
AA
Andersson
A M
AM
Petersen
J H
JH
Jensen
T K
TK
Müller
J
J
Skakkebaek
N E
NE
D000293:Adolescent; D000328:Adult; D000375:Aging; D002648:Child; D004958:Estradiol / Q000097:blood*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood*; D006801:Humans; D007265:Inhibins / Q000097:blood*; D007986:Luteinizing Hormone / Q000097:blood*; D008597:Menstrual Cycle; D011627:Puberty; D012016:Reference Values
D004958:Estradiol; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone