Premenopausal antimüllerian hormone concentration is associated with subsequent atherosclerosis

Abstract

Objective: The aim of this study was to determine if premenopausal ovarian reserve is associated with susceptibility for atherosclerosis.

Methods: Female cynomolgus macaques (n = 66, women's equivalent age = 45 y) consumed an atherogenic diet for ∼5 months before the measurement of a marker of ovarian reserve (antimüllerian hormone [AMH]), plasma lipids, follicular phase estradiol, and body weight (BW). Monkeys were then ovariectomized (OVX; n = 17), remained premenopausal (n = 20), or were induced to have reduced ovarian reserve (ROR, n = 29). After 26 additional months consuming the diet, atherosclerosis measurements and risk variables were reassessed.

Results: No differences in baseline AMH, plasma lipids, BW, and estradiol or postdiet lipids and BW were observed among the groups subsequently assigned to the OVX, premenopausal control, or reduced ovarian reserve conditions. Postdiet measurements of atherosclerosis extent did not differ among the groups. However, analysis of plaque size by tertile of baseline AMH revealed that plaques were largest in monkeys that began the experiment with the lowest baseline AMH, followed by those in the middle and high tertiles (plaque extent: low AMH, 0.76 ± 0.12 mm; mid AMH, 0.46 ± 0.1 mm; high AMH, 0.34 ± 0.08 mm; P = 0.02). Baseline AMH and plaque size were also correlated negatively (r = -0.31, P = 0.01). Plasma lipids were also correlated significantly with plaque extent (all P < 0.01) but not with AMH.

Conclusions: We report for the first time an inverse relationship between a marker of ovarian reserve (AMH) and subsequent atherosclerosis risk.

FIG. 1

A: Iliac artery atherosclerosis plaque area (mm²) among OVX (n = 17), ROR (n = 29), and PRE (n = 20) cynomolgus monkeys after ~2 years of diet consumption. B: Plaque area depicted according to tertiles of baseline plasma antimullerian hormone (AMH), all treatment groups combined. C: Plaque area depicted according to median baseline AMH for each individual treatment group. D: Correlation between baseline AMH and atherosclerosis, all treatment groups combined: OVX (○), PREMENOP (□), and ROR subset (diamond shape). Data are presented as mean ± SE plaque area (back transformed from SQRT) (A–C) and as the association between the SQRT of plaque size ± SE and SQRT of AMH (r = −0.31, P < 0.01) (D). OVX, ovariectomized; ROR, reduced ovarian reserve; PRE, premenopausal control; AMH, antimüllerian hormone; PREMENOP, premenopausal; SQRT, square root.