A systematic review of the association between modifiable lifestyle factors and circulating anti-Müllerian hormone.

Background: Levels of anti-Müllerian hormone (AMH) are known to be associated with lifestyle determinants such as smoking and oral contraception (OC) use. When measuring AMH in clinical practice, it is essential to know which factors may influence circulating levels or ovarian reserve in general.

Objective and rationale: To date, there is no systematic review or summarizing consensus of the nature and magnitude of the relation between AMH and modifiable lifestyle factors. The purpose of this review was to systematically assess the evidence on association of lifestyle behaviors with circulating AMH levels.

Search methods: We performed a pre-registered systematic review of publications in Embase and PubMed on the lifestyle factors BMI, smoking, OC use, alcohol consumption, caffeine consumption, physical activity, and waist-hip ratio (WHR) in relation to circulating AMH levels up to 1 November 2023. The search strategy included terms such as 'Anti-Mullerian hormone', 'lifestyle', and 'women'. Studies were considered eligible if the association between at least one of the lifestyle factors of interest and AMH was assessed in adult women. The quality of included studies was assessed using the Study Quality Assessment Tools of the National Heart, Lung, and Blood Institute. The results were presented as ranges of the most frequently used association measure for studies that found a significant association in the same direction.

Outcomes: A total of 15 072 records were identified, of which 65 studies were eligible for inclusion, and 66.2% of the studies used a cross-sectional design. The majority of studies investigating BMI, smoking, OC use, and physical activity reported significant inverse associations with AMH levels. For WHR, alcohol, and caffeine use, the majority of studies did not find an association with AMH. For all determinants, the effect measures of the reported associations were heterogeneous. The mean difference in AMH levels per unit increase in BMI ranged from -0.015 to -0.2 ng/ml in studies that found a significant inverse association. The mean difference in AMH levels for current smokers versus non-smokers ranged from -0.4 to -1.1 ng/ml, and -4% to -44%, respectively. For current OC use, results included a range in relative mean differences in AMH levels of -17% to -31.1%, in addition to a decrease of 11 age-standardized percentiles, and an average decrease of 1.97 ng/ml after 9 weeks of OC use. Exercise interventions led to a decrease in AMH levels of 2.8 pmol/l to 13.2 pmol/l after 12 weeks in women with polycystic ovary syndrome or a sedentary lifestyle.

Wider implications: Lifestyle factors are associated with differences in AMH levels and thus should be taken into account when interpreting individual AMH measurements. Furthermore, AMH levels can be influenced by the alteration of lifestyle behaviors. While this can be a helpful tool for clinical and lifestyle counseling, the nature of the relation between the observed differences in AMH and the true ovarian reserve remains to be assessed.

Registration number: PROSPERO registration ID: CRD42022322575.