A C de Kat1, W M M Verschuren2, M J C Eijkemans3, Y T van der Schouw3, F J M Broekmans4. 1. Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands a.c.dekat@umcutrecht.nl. 2. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands National Institute for Public Health and the Environment, 3720 BA Bilthoven, The Netherlands. 3. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. 4. Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands.
Abstract
STUDY QUESTION: Is there a relationship between serum anti-Müllerian hormone (AMH) level and cardiovascular disease (CVD) risk in premenopausal women? SUMMARY ANSWER: There are indications that premenopausal women with very low ovarian reserve may have an unfavorable CVD risk profile. WHAT IS KNOWN ALREADY: Age at menopause is frequently linked to CVD occurrence. AMH is produced by ovarian antral follicles and provides a measure of remaining ovarian reserve Literature on whether AMH is related to CVD risk is still scarce and heterogeneous. STUDY DESIGN, SIZE, DURATION: Cross-sectional study in 2338 women (age range of 20-57 years) from the general population, participating in the Doetinchem Cohort Study between 1993 and 1997. PARTICIPANTS/MATERIALS, SETTING, METHODS: CVD risk was compared between 2338 premenopausal women in different AMH level-categories, with adjustment for confounders. CVD risk was assessed through levels of systolic and diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol and glucose, in addition to a summed score of CVD risk factors. Among other factors, analyses were corrected for smoking, oral contraceptive use and BMI. MAIN RESULTS AND THE ROLE OF CHANCE: The relationship of serum AMH levels with CVD risk factor outcomes was nonlinear. Women with AMH levels <0.16 µg/l had 0.11 (95% confidence intervals (CIs) 0.01; 0.21) more metabolic risk factors compared with women with AMH levels ≥0.16 µg/l. There was no association of individual risk factor levels with AMH levels, besides a tendency towards lower total cholesterol levels of 0.11 mmol/l (95% CI -0.23; 0.01) in women with AMH levels <0.002 µg/l compared with women with AMH levels ≥0.16 µg/l. Although not statistically significant, these effect sizes were larger in women below 40 years of age. LIMITATIONS, REASONS FOR CAUTION: Causality and temporality of the studied association cannot be addressed here. Moreover, the clinical and statistical significance of the results of this exploratory study should be interpreted with caution due to the absence of adjustment for multiple statistical testing. WIDER IMPLICATIONS OF THE FINDINGS: This population-based study supports previous findings that premenopausal women with very low AMH levels may have an increased CVD risk. It lays the groundwork for future research to focus on this group of women. Longitudinal studies with more sensitive AMH assays may furthermore help better understand the implications of these results. STUDY FUNDING/COMPETING INTEREST: No financial support was received for this research or manuscript. The Doetinchem Cohort Study is conducted and funded by the Dutch National Institute for Public Health and the Environment F.J.M.B. has received fees and grant support from Merck Serono, Gedeon Richter, Ferring BV and Roche. TRIAL REGISTRATION NUMBER: N/A.
STUDY QUESTION: Is there a relationship between serum anti-Müllerian hormone (AMH) level and cardiovascular disease (CVD) risk in premenopausal women? SUMMARY ANSWER: There are indications that premenopausal women with very low ovarian reserve may have an unfavorable CVD risk profile. WHAT IS KNOWN ALREADY: Age at menopause is frequently linked to CVD occurrence. AMH is produced by ovarian antral follicles and provides a measure of remaining ovarian reserve Literature on whether AMH is related to CVD risk is still scarce and heterogeneous. STUDY DESIGN, SIZE, DURATION: Cross-sectional study in 2338 women (age range of 20-57 years) from the general population, participating in the Doetinchem Cohort Study between 1993 and 1997. PARTICIPANTS/MATERIALS, SETTING, METHODS: CVD risk was compared between 2338 premenopausal women in different AMH level-categories, with adjustment for confounders. CVD risk was assessed through levels of systolic and diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol and glucose, in addition to a summed score of CVD risk factors. Among other factors, analyses were corrected for smoking, oral contraceptive use and BMI. MAIN RESULTS AND THE ROLE OF CHANCE: The relationship of serum AMH levels with CVD risk factor outcomes was nonlinear. Women with AMH levels <0.16 µg/l had 0.11 (95% confidence intervals (CIs) 0.01; 0.21) more metabolic risk factors compared with women with AMH levels ≥0.16 µg/l. There was no association of individual risk factor levels with AMH levels, besides a tendency towards lower total cholesterol levels of 0.11 mmol/l (95% CI -0.23; 0.01) in women with AMH levels <0.002 µg/l compared with women with AMH levels ≥0.16 µg/l. Although not statistically significant, these effect sizes were larger in women below 40 years of age. LIMITATIONS, REASONS FOR CAUTION: Causality and temporality of the studied association cannot be addressed here. Moreover, the clinical and statistical significance of the results of this exploratory study should be interpreted with caution due to the absence of adjustment for multiple statistical testing. WIDER IMPLICATIONS OF THE FINDINGS: This population-based study supports previous findings that premenopausal women with very low AMH levels may have an increased CVD risk. It lays the groundwork for future research to focus on this group of women. Longitudinal studies with more sensitive AMH assays may furthermore help better understand the implications of these results. STUDY FUNDING/COMPETING INTEREST: No financial support was received for this research or manuscript. The Doetinchem Cohort Study is conducted and funded by the Dutch National Institute for Public Health and the Environment F.J.M.B. has received fees and grant support from Merck Serono, Gedeon Richter, Ferring BV and Roche. TRIAL REGISTRATION NUMBER: N/A.
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