Context:
Ovarian dysfunction is classically categorized on the basis of cycle history, FSH, and estradiol levels. Novel ovarian markers may provide a more direct insight into follicular quantity in hypergonadotropic women.

Objective:
The objective of the study was to investigate the distribution of novel ovarian markers in young hypergonadotropic women as compared with normogonadotropic regularly menstruating women.

Design:
This was a nationwide prospective cohort study.

Setting:
The study was conducted at 10 hospitals in The Netherlands.

Patients:
Women below age 40yr with regular menses and normal FSH (controls; n=83), regular menstrual cycles and elevated FSH [incipient ovarian failure (IOF); n=68]; oligomenorrhea and elevated FSH [referred to as transitional ovarian failure (TOF); n=79]; or at least 4 months amenorrhea together with FSH levels exceeding 40IU/liter [premature ovarian failure (POF); n=112].

Main Outcome Measures:
Serum levels of anti-Müllerian hormone (AMH), inhibin B, and antral follicle count (AFC) was measured.

Results:
All POF patients showed AMH levels below the fifth percentile (p5) of normoovulatory women. Normal AMH levels (>p5) could be identified in 75% of IOF, 33% of TOF patients, and 98% of controls. AFC and AMH levels changed with increasing age (P<0.0001), whereas inhibin B did not (P=0.26). AMH levels were significantly different between TOF and IOF over the entire age range, whereas AFC became similar for TOF and IOF at higher ages.

Conclusions:
Compared with inhibin B and AFC, AMH was more consistently correlated with the clinical degree of follicle pool depletion in young women presenting with elevated FSH levels. AMH may provide a more accurate assessment of the follicle pool in young hypergonadotropic patients, especially in the clinically challenging subgroups of patients with elevated FSH and regular menses (i.e. IOF) and in hypergonadotropic women with cycle disturbances not fulfilling the POF diagnostic criteria (i.e. TOF) (Fig 2).

Figure 2: Individual AMH levels (log scale) in relation to age in regularly menstruating controls and three subgroups of patients with elevated FSH levels. The black lines indicate the P5 value for age. The +++++ lines indicate the menopausal threshold value for AMH (0.086μg/ml); the dashed lines indicate the lower level of detection of the AMH assay (0.023μg/ml) (24). (Reprinted from Knauff EAH, Eijkemans MJC, Lambalk CB, et al. Anti-Müllerian hormone, inhibin b, and antral follicle count in young women with ovarian failure. J Clin Endocrinol Metab. 2009;94:786-792, with permission from The Endocrine Society.)