Obesity, Insulin Resistance, and Hyperandrogenism Mediate the Link between Poor Diet Quality and Ovarian Dysmorphology in Reproductive-Aged Women

Abstract

The relationship between diet quality and ovarian morphology has biological plausibility yet remains unclear and was therefore evaluated. In a multicenter cross-sectional analysis, four dietary patterns were scored for 111 consecutive reproductive-aged women (18–45 years) using (1) Healthy Eating Index (HEI-2015); (2) alternative HEI-2010; (3) alternate Mediterranean Diet (aMED); (4) and Dietary Approaches to Stop Hypertension (DASH) indices. Ovarian volume (OV) and follicle number per ovary (FNPO) were evaluated on transvaginal ultrasonography. Relationships between dietary and ovarian morphology indices were evaluated by linear regression and mediation analyses. Associations between aMED and DASH scores and OV/FNPO were completely mediated by obesity, insulin resistance, and hyperandrogenism (All: p < 0.05), unlike direct associations (All: p ≥ 0.89). Namely, a 1-standard deviation [SD] increase in aMED score was associated with decreases in OV (0.09 SD; 0.4 mL) through reducing waist circumference. Likewise, a 1 SD increase in aMED and DASH score was associated with decreases in OV (0.07 SD; 0.3 mL) by reducing glucose response to a 75 g glucose tolerance test. A 1 SD increase in DASH score was associated with decreased FNPO (0.07 SD; 2 follicles) by reducing free androgen index (All: p < 0.05). Adherence to aMED and DASH eating plans was indirectly associated with significant improvements in ovarian form, providing novel mechanistic insights for future interventions about contributions of diet quality on ovarian function.

Impact of Obesity on Anti-Mullerian Hormone (AMH) Levels in Women of Reproductive Age

“…Obesity remains a persistent and growing public health concern, with current rates nearing 40% of reproductive-aged women in the United States [ 1 ]. Obesity impacts a broad array of health risks in women across the lifespan [ 2 ], including adverse reproductive health outcomes such as menstrual cycle irregularity, abnormal uterine bleeding, endometrial hyperplasia, infertility, and pregnancy complications [ 3 , 4 , 5 , 6 , 7 ]. Furthermore, women with obesity are 20% more likely to experience later onset of menopause, which in part may underlie the increased risk of breast, ovarian, and uterine cancer seen in this population [ 8 ].…”

“…To that end, an altered ovarian follicular environment has been confirmed in women with obesity and involves disruptions in multiple systems, including steroidogenic action, metabolism, and inflammation, all of which can impact folliculogenesis and ovulatory potential [ 18 ]. The degree to which obesity impacts ovarian reserve is more controversial as available data have largely focused on sub- or infertile populations, wherein studies have not shown consistent associations between serum markers of ovarian reserve and body mass index (BMI) [ 4 , 19 ]. Anti-Mullerian hormone (AMH), a glycoprotein primarily produced by the granulosa cells of primary and early-stage antral follicles, is a marker whose association with obesity is controversial [ 20 , 21 , 22 ]—albeit a single meta-analysis suggests a negative association of AMH with BMI [ 19 ].…”

Impact of Increased Oxidative Stress on Cardiovascular Diseases in Women With Polycystic Ovary Syndrome

“…For instance, Kazemi et al. have evaluated the relationship between four dietary patterns and the overall ovarian function, and found that the latter was affected by diets that influence obesity, metabolic status and hyperandrogenism regulation ( 176 ). The Dietary Approaches to Stop Hypertension (DASH) eating plan has also been previously analyzed by Asemi and colleagues, who highlighted the effect of the DASH diet not only on lipid profiles, but also on oxidative stress markers in PCOS women.…”

Obesity, but not hyperandrogenism or insulin resistance, predicts skeletal muscle mass in reproductive‐aged women with polycystic ovary syndrome: A systematic review and meta‐analysis of 45 observational studies

“…Many studies have focused on obesity in women with PCOS by characterizing excessive fat mass (quantity) in a predominantly android fat distribution and impaired fat function (quality). [3][4][5][6][7][8] Accordingly, the adverse effects of altered fat tissue on cardiometabolic 6,[9][10][11][12][13][14] and reproductive [15][16][17][18] complications have been established in PCOS.…”

“…Difficulties also exist in establishing an accurate definition of PCOS status owing to a reliance on a self-reported diagnosis that is unreliable likely leading to misdiagnosis, 35,[57][58][59] unreliable measures of androgen status, 60 and/or ovarian morphology. 18,61,62 Variability in defining control cohorts and heterogeneity in groups' ethnic composition 27 may be contributory.…”