Basal and dynamic relationships between serum anti-Müllerian hormone and gonadotropins in patients with functional hypothalamic amenorrhea, with or without polycystic ovarian morphology

Abstract

Background To evaluate in women with functional hypothalamic amenorrhea (FHA), whether there is a difference between patients with and without polycystic ovarian morphology (PCOM) concerning the response to a gonadotropin releasing hormone (GnRH) stimulation test and to pulsatile GnRH treatment. Methods In a retrospective observational study, 64 women with FHA who underwent a GnRH stimulation test and 32 age-matched controls without PCOM were included. Pulsatile GnRH treatment was provided to 31 FHA patients and three-month follow-up data were available for 19 of these. Results Serum levels of gonadotropins and estradiol were lower in FHA women than in controls (p < 0.05). FHA patients revealed PCOM in 27/64 cases (42.2%). FHA patients without PCOM revealed lower anti-Müllerian hormone (AMH) levels than controls (median 2.03 ng/mL, IQR 1.40–2.50, versus 3.08 ng/mL, IQR 2.24–4.10, respectively, p < 0.001). Comparing FHA patients with and without PCOM, the latter revealed lower AMH levels, a lower median LH increase after the GnRH stimulation test (240.0%, IQR 186.4–370.0, versus 604.9%, IQR 360.0–1122.0; p < 0.001) as well as, contrary to patients with PCOM, a significant increase in AMH after three months of successful pulsatile GnRH treatment (median 1.69 ng/mL at baseline versus 2.02 ng/mL after three months of treatment; p = 0.002). Conclusions In women with FHA without PCOM, the phenomenon of low AMH levels seems to be based on relative gonadotropin deficiency rather than diminished ovarian reserve. AMH tended to rise after three months of pulsatile GnRH treatment. The differences found between patients with and without PCOM suggest the former the existence of some PCOS-specific systemic and/or intra-ovarian abnormalities.

Serum LH levels are associated to serum insulin and Anti‐Müllerian hormone levels in women with both functional hypothalamic amenorrhoea and polycystic ovarian morphology

“…The prevalence of PCOM in our FHA population was even higher than that in the general population where it is between 7% and 24% according to the literature 6,9–14 . This finding has been reported by others, as reviewed in, 8 and in a more recent study 15 . Our previous study did not allow us to explain clearly such a prevalence of PCOM in FHA.…”

“…6,[9][10][11][12][13][14] This finding has been reported by others, as reviewed in, 8 and in a more recent study. 15 Our previous study did not allow us to explain clearly such a prevalence of PCOM in FHA. Interestingly, we found a strong positive correlation between the body mass index (BMI) and serum LH level exclusively in women with FHA and PCOM.…”

Stress and polycystic ovarian morphology in functional hypothalamic amenorrhea: a retrospective cohort study

“…This retrospective cohort study was conducted at the Clinical Division of Gynecologic Endocrinology and Reproductive Medicine of the Medical University of Vienna, Austria. We estimated that the prevalence of PCOM would be 40% in our FHA population [ 2 ] and that stress would increase the prevalence of PCOM (55% versus 25%). With these estimates, a sample size of 38 patients per group would be necessary to detect a difference in stress-associated FHA-PCOM relative to exercise-associated FHA (power 95%, alpha = 0.05).…”

“…Thus, 76 FHA women (38 “stress-associated”, 38 “excessive exercise”) were included from January 2017 – March 2022. As previously described [ 2 , 3 , 6 ], a strict FHA definition was used (also see Table 1 ): secondary amenorrhea for at least six months and a negative progestogen challenge test with context of intense physical activity or notion of recent psychological stress, confirmed by a psychologic report. Pregnancy, hypothyroidism, and hyperprolactinemia and any organ-related pituitary dysfunction had to be excluded.…”

“…On the same day, a vaginal ultrasound was performed with an “Aloka Prosound 6” ultrasound machine and an “UST-9124 Intra Cavity transducer” (frequency range 3.0–7.5 MHz; Wiener Neudorf, Austria). PCOM, the main outcome parameter, was defined as when the number of follicles per ovary exceeded 12 [ 2 , 3 ]. In addition, the following basic patient characteristics were also included: age at evaluation, body mass index (BMI), and the duration of amenorrhea.…”