The ovarian markers of the FSH insufficiency in functional hypothalamic amenorrhoea

The purpose of this work was to revisit the gonadotrophin insufficiency of functional hypothalamic amenorrhoea (FHA) with the use of relevant ovarian markers.

Serum anti-Mullerian hormone (AMH), estradiol (E2), inhibin B, LH and FSH were immunoassayed in 31 women with FHA and in 30 healthy women in early follicular phase. The ovarian antral follicle number (FN) was determined within two distinct diameter ranges (2-5 and 6-9 mm) by ultrasound in real time, the same day as the blood sampling.

The 2-5 mm FN was similar between the two groups, while the 6-9 mm FN was significantly less in FHA than in controls, in relation with lower serum FSH levels (r=0.428; P<0.024). Nine (29%) FHA patients had a low serum basal FSH level (i.e. <4.5 IU/l, 5th percentile of control values). In the 22 (71%) patients with apparently normal FSH, the mean 6-9 mm FN was similar to controls. However, in this sub-group, the mean AMH serum level and the AMH:2-5 mm FN ratio were significantly higher and the mean inhibin B serum level was significantly lower than in controls. No significant relationship was found between the serum LH levels and the FN, AMH or inhibin B values.

Only a minority of patients with FHA have a low serum basal FSH level, and we show that this is associated with fewer 6-9 mm follicles at the ovarian level. Despite a normal serum FSH level and 6-9 mm FN in the majority of patients with FHA, the functional follicle markers are abnormal. This suggests that the FSH action on the ovary is incomplete and is not properly reflected by its serum level nor by FN at ultrasound.