Antimüllerian hormone levels are lower in BRCA2 mutation carriers

Abstract

Objective To compare Anti-Mullerian Hormone (AMH) levels in women at high risk for hereditary breast and ovarian cancer compared to healthy, low-risk controls. Design Prospective cohort Setting Ambulatory Patient(s) Reproductive age women with a uterus and both ovaries were analyzed in four groups: BRCA1 carriers, BRCA2 carriers, BRCA negative, and low-risk controls Intervention(s) Self-collected dried blood spot (DBS) Main Outcome Measure(s) AMH levels Result(s) One hundred ninety-five women were included: 55 BRCA1 carriers, 50 BRCA2 carriers, 26 BRCA negative, and 64 low-risk controls. After adjusting for confounders, BRCA2 carriers had AMH levels that were 33% lower than controls (Geometric Mean Ratio(GMR)=0.67, 95% CI 0.47–0.94) and an increased odds of having AMH<1 ng/mL (OR 3.69, 95% CI 1.34–10.19). BRCA1 carriers and BRCA negative women had similar AMH levels to controls. When analysis was restricted to regularly menstruating women younger than 40, BRCA2 carriers continued to demonstrate significantly lower AMH levels and increased likelihood of low AMH. Also, in this restricted group, BRCA negative women demonstrated AMH levels that were 42% lower than controls (GMR=0.58; 95%CI 0.35–0.95). No difference in AMH was observed among BRCA1 carriers. Conclusion(s) We observed significantly lower AMH levels among BRCA2 carriers compared to low-risk controls. These results were stable across all models. BRCA negative women also had lower AMH values, but only in models restricted to young, regularly menstruating women. In contrast to previous analyses, BRCA1 carriers had AMH values that were similar to low-risk controls, but this may be due to differences in the population studied.

Impact of BRCA1 and BRCA2 mutations on ovarian reserve and fertility preservation outcomes in young women with breast cancer

“…Even if some evidence showed a reduction in the AMH level even in BRCA2 mutation carrier patients, this reduction has proved to be not significant [24]. Three other studies obtained a similar result: A significant difference in AMH levels between BRCA1 carriers but no BRCA2 and control was found in Philips, Wang, and Johnson's studies [3,24,25].…”

Clinical application of serum anti-Müllerian hormone in women

“…A cross-sectional study of women with a family history of breast cancer showed significantly low AMH levels in BRCA1 mutation carriers but not in BRCA2 mutation carriers [92]. In contrast, Johnson et al [93] reported that carriers of the BRCA2 mutation had more decreased AMH levels than noncarriers. Meanwhile, Michaelson-Cohen et al [94] showed no significant differences in AMH levels between BRCA1/2 mutation carriers and the general population.…”

Risk of cancer in infertile women: analysis of US claims data

“…Another potential common mechanism between cancer and infertility is the presence of mutations in genes associated with DNA repair (e.g. BRCA) that may increase the risk of both conditions (Giordano et al, 2016;Johnson et al, 2017). In summary, our findings suggest an association between infertility and higher risk of cancer compared to a population deemed by claimsbased criteria to be non-infertile.…”