Hagir Shalal MBBS, Harris E. Phillip BSc, MSc, FRCOG, FACOG, DM, LLM

*Corresponding Author: Harris E. Phillip, Obstetrician and Gynaecology consultants, Gibraltar

Cardiovascular disease is the leading cause of death for women, it is responsible for more than 33 % of mortality. Menopause does not cause cardiovascular diseases. However, there is an overall increase in heart attacks among women 10 years after menopause. This could be attributed to a decline in the natural ovarian hormones estrogen and progesterone.

For this reason, we read with interest the paper by Başak Gṻler et al immediately contemplating the value of such a tool in rendering efficient antenatal and postnatal care to women. We were specifically drawn to the conclusion that the decreased AMH levels in obese patients are a risk factor for cardiovascular disease. We found it interesting that the paper was not clear on the timing (the trimester in which the AMH values were checked), this we believe is important not only because it would lend itself to the repeatability of the study; but there is evidence to suggest that AMH values are the highest in the first trimester and then declines as pregnancy advances [1,2].

AMH is a marker of ovarian reserve, in terms of follicular numbers not necessarily the quality of the follicles. During ovarian aging, there is a gradual decline in both the quality and quantity of the ovarian follicle pool which can be influenced by genetic, autoimmune, vascular, and toxic factors, [3,4] and parity. 64.9 % of the patients in the obese group were multiparous, hence large differences in the ovarian reserve are likely to exist in women of the same age.

In the study, the authors indicated that Age and Systolic blood pressure had a significantly high predictive value for cardiovascular disease in both the obese and non-obese pregnant patient cohort. In the obese group, a low AMH level was associated with the risk of cardiovascular disease [5]. Although pregnancy can be considered a vascular stress test that may unmask a woman’s tendency to develop cardiovascular disease later in life [6], this is a brave conclusion. Our concern is based on several issues (a) in the obese patient, the AMH value ranged from 1.29±0.91ng/ml whilst in the non-obese group the AMH value ranged from 1.74 ±1.00 ng/ml., clearly revealing an overlap in the values. The measure of significance was defined as a p-value < 0.05. No correlation coefficient value was given to indicate the strength of the significance, but a glimpse of the strength may be appreciated by reviewing the p- value associated with the logistic regression analysis. Multivariate logistic regression analysis in  the obese group revealed a p-value of

0.001 when looking at the impact of age on cardiovascular disease, a p- value of 0.002 was reported for systolic blood pressure but a p-value of only 0.049 for a low AMH. Conclusions drawn from multivariate analysis are more accurate and nearer to real-life situations. The predictive value of a low AMH and its association with the risk of cardiovascular disease in obese patients is uncomfortably weak but it may be an indication of cardiovascular disease. Obesity impacts negatively on granulosa cell function [7], as evidenced by increasing numbers of anovulatory cycles among the obese female population. The resulting dysfunction in the granulosa cells leads to a reduction in AMH production but simultaneously, obesity is associated with cardiovascular risk factors which may interfere with the ovarian circulation [8], and the insult would enhance ovarian aging, leading to a further reduction in AMH levels.

Would it therefore not be more accurate to consider a low AMH to be an indication (maybe early) of cardiovascular disease as opposed to a risk factor for cardiovascular disease? Should this be so, it would allow for a relatively timely intervention in terms of lifestyle changes to delay a potential cardiovascular event, and herein lies the value of this study.

We advise caution in drawing this conclusion that a low AMH level is associated with the risk of cardiovascular disease in obese pregnant patients based on this study, The significance of a low AMH and the purported risk of cardiovascular disease in this study is weak, the sample size is small, there is a risk of bias, the absence of a universally agreeable definition of a low AMH and the lack of clarity/standardizatio n of the timing during pregnancy when the AMH value was determined concerns us. It is also unfortunate that this study was undertaken in a non-universally extrapolatable state, pregnancy, even among women, since it limits its usefulness.

 References

1. Massé V, Ferrari P, Boucorian I, Delotte J, Isnard V, et al. (2011) Normal serum concentrations of AMH in a population of fertile women in their first trimester of pregnancy. Human Reprod. 26(12): 3431 -3436.
2. Nelson SM, Stewart F, Fleming R, Freeman DJ (2010) Longitudinal assessment of AMH during pregnancy relationship with maternal adiposity, insulin and adiponectin. Fertil Steril. 93(4): 1356 -1358.
3. Voorhuis M, Onland-Moret NC, van der Schouw YT, Fauser BC, Broekmans FJ (2010) Human Studieson genetics of the age at natural menopause: a systematic review. Hum Reprod Update. 16(4): 364-377.
4. Lambalk CB, van Disseldorp J, de Koning CH, Broekmans FJ (2009) Testing ovarian reserve to predict age at menopause. Maturitas. 63(4): 280 -291.
5. Gṻler B, Özler S, Kadioğlu N, Özkan E, Gṻngören MS, et al. (2020) Is the low AMH level associated with the risk of cardiovascular disease in obese pregnants? J Obstet Gynaecol. 40(7): 912-917.
6. van Rijn BB, Nijdam ME, Bruinse HW, Roest M, Uiterwaal CS, et al. (2013) cardiovascular disease risk factors in women with a history of early-onset preeclampsia. Obstet Gynecol. 121(5): 1040- 1048.
7. Santoro N, Lasley B, McConnell D, Allsworth J, Crawford S, et al. (2004) Body size and ethnicity are associated with menstrual cycle alterations in womenin the early menopausal transition: the study of women’s Health across the nation (SWAN)daily Hormone study. J Clin Endocrinol Metab. 89(6): 2622-2631.
8. Verit FF, Akyol H, Sakar MN (2016) Low antimullerian hormone levels may be associated with cardiovascular risk markers in women with diminished ovarian reserve. Gynecological Endocrinology. 32(4): 302-305.