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Author ORCID Identifier

https://orcid.org/0000-0002-3698-1942

AccessType

Campus-Only Access for Five (5) Years

Document Type

dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Public Health

Year Degree Awarded

2021

Month Degree Awarded

May

First Advisor

Elizabeth R. Bertone-Johnson

Second Advisor

Brian W. Whitcomb

Third Advisor

Katherine W. Reeves

Fourth Advisor

Lynnette L. Sievert

Subject Categories

Epidemiology

Abstract

Anti-Müllerian hormone (AMH) has been established as a marker of ovarian age and time to menopause. AMH, a glycoprotein produced by granulosa cells of primary follicles, is detectable at birth, increases slightly until puberty, and remains relatively consistent in the early reproductive years. Importantly, AMH levels gradually decline with increasing age and are undetectable after menopause. Studies have shown that premenopausal women with higher levels of AMH are likely to experience later age at menopause. With later age at menopause being an established risk factor for breast cancer, it is hypothesized that higher levels of premenopausal AMH may be associated with increased breast cancer risk. Menopause timing has also been associated with established breast cancer risk factors including parity, breastfeeding, and increased adiposity. This dissertation evaluated the association of AMH levels with breast cancer risk and how AMH is related to breast cancer risk factors. The relationship of reproductive and anthropometric factors with AMH were examined among 1,618 participants in the Nurses’ Health Study II. Furthermore, the association of AMH with breast cancer risk was evaluated among 1,529 premenopausal and perimenopausal women in the Study of Women’s Health Across the Nation. In our first analysis utilizing data from Nurses’ Health Study II, we observed that parity was positively associated with higher AMH levels, but not after adjusting for breastfeeding. Longer cumulative breastfeeding duration was associated with higher AMH levels even accounting for parity. Furthermore, longer cumulative breastfeeding duration was positively associated with age at menopause, but not after adjusting for AMH levels. Findings suggest that AMH largely mediates the relation of breastfeeding with age at menopause. In our second analysis in Nurses’ Health Study II, higher BMI, waist circumference, and weight gain between age 18 and mid-adulthood were inversely associated with AMH levels. These results provide further evidence that adiposity may be associated with menopause timing. In our third analysis utilizing data from Study of Women’s Health Across the Nation, we observed a non-significant positive association with breast cancer risk. Our summary estimates were in line with previous prospective studies, suggesting that women with higher AMH levels are at higher risk for breast cancer. In conclusion, we found that reproductive factors and adiposity are associated with AMH levels in mid-late reproductive-aged women. In addition, AMH levels, an established marker for menopause timing, was associated with breast cancer risk in late reproductive-aged women. Due to theses complex relations, further studies are needed to better understand the biological mechanisms underlying the associations of AMH, menopause timing, and breast cancer.

DOI

https://doi.org/10.7275/22470560.0

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