Lack of Serum anti-Mullerian hormone responses after recombinant human chorionic gonadotropin stimulation in women with polycystic ovary syndrome

Abstract

Context: Polycystic ovary syndrome (PCOS) is an anovulatory disorder characterized by excess androgen production and increased LH secretion. Serum anti-Mullerian hormone (AMH) is also elevated in this disorder. Women with PCOS exhibit a positive correlation between AMH and LH levels and recent in vitro data demonstrate that LH can directly stimulate AMH production by granulosa cells from women with PCOS.

Objective: The objective of the study was to directly test whether LH increases AMH production in women with PCOS in vivo by assessing responses after recombinant human chorionic gonadotropin (r-hCG) stimulation.

Design: This was a prospective study.

Setting: The study was conducted at a research center at an academic medical center.

Participants: Women with PCOS (n = 28) and normal controls (n = 29) participated in the study.

Interventions: Blood samples were obtained before and 24 hours after iv administration of 25 μg r-hCG.

Main outcome measures: Basal and stimulated serum AMH, androstenedione, T, and 17-hydroxyprogesterone levels were measured.

Results: Baseline AMH levels in women with PCOS were greater than in normal controls and correlated with levels of LH as well as androstenedione, T, and 17-hydroxyprogesterone. A rise of serum AMH levels was not observed after r-hCG administration in women with PCOS or normal ovaries.

Conclusion: These findings are in contrast to in vitro evidence demonstrating that AMH secretion by granulosa cells of PCOS women in response to LH stimulation and suggest AMH regulation in vivo is complex and that the elevated serum AMH in women with PCOS is not a direct effect of the excess LH production characteristic of PCOS.

Trial registration: ClinicalTrials.gov NCT00747617.

Figures

Figure 1.

AMH levels are elevated in PCOS subjects before stimulation. A, Graph comparing mean (±SE) serum AMH levels at baseline in PCOS and normal women. B, Graph comparing the mean (±SE) serum AMH per antral follicle in the subset of PCOS (n = 12) and normal (n = 10) women who underwent three-dimensional ovarian ultrasonography for an accurate determination of antral follicle count. CTRL, control.

Figure 2.

AMH levels positively correlate with LH and androgen levels in PCOS subjects before stimulation. Graphs in which the baseline AMH level for each PCOS subject and normal control is plotted against LH, BMI, age, A4, and total T for each subject at baseline are shown (r = Spearman rho). CTRL, control.

Figure 3.

Stimulation with r-hCG results in significant increases in androgen levels in PCOS subjects and normal women. Graphs comparing the mean (±SE) serum 17-OHP, A4, and T levels before and 24 hours after stimulation with 25 μg r-hCG iv in PCOS and normal women. *, P value comparing the change in androgen levels in PCOS vs controls. CTRL, control.

Figure 4.

Stimulation with r-hCG does not result in detectable increases in AMH levels in PCOS subjects or normal women. A, Graph comparing the mean (±SE) serum AMH levels before and 24 hours after stimulation with 25 μg r-hCG iv in PCOS and normal women. B, Graph comparing the mean (±SE) serum AMH levels before and 24 and 48 hours after stimulation with a higher dose of 250 μg r-hCG iv in PCOS and normal women. CTRL, control.