Secondary Logo

Journal Logo

Original Article

Correlation Between Serum AMH Levels and Cardiometabolic Indices in PCOS Women

Mitra, Subarna,; Saharia, Gautom K.1; Jena, Saubhagya K.

Author Information
Indian Journal of Endocrinology and Metabolism: Nov–Dec 2021 - Volume 25 - Issue 6 - p 545-550
doi: 10.4103/ijem.ijem_421_21
  • Open



Polycystic ovary syndrome (PCOS) is the most common endocrinopathy encountered in women of child-bearing age with several long-term cardiometabolic sequel like insulin resistance (IR), metabolic syndrome (MS), type 2 diabetes mellitus, and coronary artery disease (CAD).[123] Menopausal transition is characterized by declining ovarian reserve and function, and the time of menopause is determined by the inevitable decline of the ovarian follicle pool. Serum anti-Mullerian hormone (AMH), a glycoprotein secreted by the granulosa cells of the preantral and antral follicles of the ovary,[45] has emerged as a promising single marker of reproductive ageing.[67] Peri- and postmenopausal life stages are associated with deterioration of cardiovascular health.[68] This is attributed to declining estrogen levels which in turn impacts lipid profile and coronary artery dynamics, thus playing a crucial role in the appearance and progression of subclinical CAD.[9] There is growing research whether decreased AMH may serve as an early indicator of worsening cardiometabolic status. Studies in general premenopausal women have demonstrated that lower AMH levels may portend a more unfavorable cardiometabolic health.[810] Whether AMH relates to cardiometabolic markers differently in women with PCOS, a high risk group for future cardiovascular and metabolic disorders, is still uncertain. Compared to controls, AMH concentrations are higher in PCOS, and age-related decline in AMH levels is slower culminating in delayed ovarian ageing and longer reproductive lifespan.[111213141516171819202122232425] However, whether these higher levels of AMH affect or predict overall cardiovascular risk in PCOS, remains unclear as results from existing studies are conflicting. Obesity, high AMH, IR, and MS, though not in the diagnostic criteria of PCOS, are closely associated with this condition, but the precise association between AMH and metabolic disturbances is yet to be elucidated. Furthermore, MS, a harbinger of CAD, presents at an earlier age in PCOS. Therefore, early identification of potential biomarkers, long before menopause sets in, will help in stratification of CAD risk and encourage disease prevention in this high-risk population. Despite evidence of higher prevalence of PCOS as well as MS and CAD in South Asian women compared to other ethnicities, studies investigating the relationship between serum AMH levels and MS in Indian women with PCOS are scarce.

Therefore, this study was undertaken to elucidate the correlation between AMH levels and various cardiometabolic parameters in PCOS women of the reproductive age group in eastern India. We also sought to compare AMH levels in PCOS women with and without MS.


This cross-sectional study was conducted at a tertiary care center in eastern India from January 2019 to December 2020. All women between 20 and 40 years of age diagnosed with PCOS were included after informed consent. Diagnosis of PCOS was established if woman fulfilled two out of three features in the Rotterdam 2003 criteria, i.e., chronic anovulation/oligoovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovaries (PCO) on ultrasound (USG).[1] Those with cycle intervals of <21 days or >35 days, or <8 cycles per year were considered to have ovulatory dysfunction. Women with acne, hirsutism with modified Ferriman–Gallwey score ≥8, and/or androgenic alopecia were considered to have clinical hyperandrogenism. Serum testosterone levels ≥80 ng/dL was indicative of biochemical hyperandrogenism. Polycystic ovarian morphology (PCOM) was defined as ovarian volume >10 cc. Those with menarche within 3 years before enrollment; history of use of any hormones like oral contraceptives, antiandrogens, ovulation induction agents, antidiabetic or lipid lowering agents in the last 3 months; conditions likely to decrease AMH levels like previous chemotherapy, ovarian surgery and/or pelvic irradiation were excluded. IEC approval was obtained on 6th Dec 2018.

Sample size was calculated based on correlation coefficients between the components of MS and AMH levels, taken from a previous study.[26] A total of 144 women were recruited. All participants were categorized into one of the four phenotypes as per Rotterdam criteria – phenotype A/frank PCOS, phenotype B/non-PCO PCOS, phenotype C/ovulatory PCOS, and phenotype D/normoandrogenic PCOS. History was elicited pertaining to age, menstrual pattern, androgenic symptoms, and parity. Clinical examination was performed to identify acne, hirsutism, androgenic alopecia, and acanthosis nigricans. Their height, weight, body mass index (BMI), waist circumference (WC), waist: hip circumference ratio, and systolic and diastolic blood pressure (BP) were recorded. Weight was measured using a digital scale to the nearest 100 g, with the women dressed in light clothing and barefoot. Height was determined using a tape measure, with the women standing upright, barefoot, with their shoulders aligned normally. Those with BMI ≥23 kg/m2 and ≥25 kg/m2 were considered to be overweight and obese, respectively. Waist and hip circumference were measured as per the WHO STEPS (STEPwise approach to noncommunicable disease risk factor surveillance) protocol, wherein WC was measured at the approximate midpoint between the lower margin of the last palpable rib and the top of the iliac crest at the end of a normal expiration, while hip circumference was measured around the widest portion of the buttocks, using a stretch-resistant tape that wrapped snugly but not constricting and held parallel to the floor. USG was performed either transvaginally or transabdominally depending upon marital status. Since determination of follicle number per ovary (FNPO) by transabdominal USG can be unreliable, especially in obese or unmarried women, ovarian volume was measured in all cases rather than FNPO.

Blood was collected from the antecubital vein of all participants under all aseptic conditions on days 2–4 of the spontaneous menstrual cycle or on any day for women with amenorrhea after overnight fasting of 8–12 h. Serum was analyzed for total testosterone and insulin by the chemiluminescence method in Siemens Advia Centaur XP immunoassay analyzer. Serum fasting lipid profile and fasting plasma glucose were estimated by Beckmann Coulter AU5800 autoanalyzer using reagents from Beckmann Coulter, Inc., USA. Quality control in both the analyzers were maintained by using Bio-Rad internal quality control samples daily and external quality control monitored by monthly samples from the Association of Clinical Biochemists of India prepared by Christian Medical College, Vellore. For analysis of AMH, the serum samples were stored at temperature of -80 °C. The analysis was later performed by the ELISA-based kit method from Epitope Diagnostics, Inc., San Diego, USA.

IR was defined as homeostasis model assessment-insulin resistance (HOMA-IR) value >2.5, as calculated by the formula HOMA-IR = [fasting insulin (μU/mL) × fasting glucose (mg/dL)]/405. MS was diagnosed if any three of the following five risk factors are present as per the cutoffs for Asian Indians – WC >80 cm, triglycerides (TG) ≥150 mg/dL, high-density lipoprotein cholesterol (HDL-C) <50 mg/dL, systolic BP ≥130 mmHg and/or diastolic BP ≥85 mmHg, and fasting glucose ≥100 mg/dL.[27] The clinico-endocrine profile was compared between those with MS and those without MS.

Statistical analysis

The statistical analysis was performed using IBM SPSS Statistics 20.0 for Windows. Normality of data was established by Kolmogorov–Smirnov test. Continuous and categorical variables were expressed as mean ± SD and frequency with percentages, respectively. Pearson's correlation coefficient was used for assessing the correlation between serum AMH levels and cardiometabolic risk factors. Student's t-test was employed for comparison of continuous variables, while Chi-square test was used for comparing proportions between MS and non-MS groups. P value < 0.05 was considered as statistically significant.


Table 1 summarizes the baseline characteristics of the study participants. The mean age of the participants was 24.73 ± 3.37 years. Almost two-third of the participants (69.4%) were overweight/obese with a mean BMI of 25.58 ± 4.71 kg/m2. Only eight women had no menstrual abnormality. Majority of them (70.8%) had clinical and/or biochemical hyperandrogenism. Acanthosis nigricans, a clinical indicator of IR, was found in 45.8% women, but biochemical IR, as estimated by HOMA-IR >2.5, was observed only in 18 subjects (12.5%). Nearly one-third had MS (31.3%). Mean AMH levels were 11.51 ± 5.52 ng/mL.

Table 1:
Clinicometabolic characteristics of women with PCOS

No correlation was observed between AMH and components of MS as well as with other cardiometabolic parameters, as shown in Table 2. However, there was a significant positive correlation of AMH with ovarian volume and testosterone levels and negative correlation with age.

Table 2:
Correlation between AMH and cardio-metabolic parameters

Table 3 depicts the clinicometabolic profile of PCOS women with and without MS. Hirsutism, obesity, and acanthosis nigricans were more prevalent MS group, while menstrual dysfunction was more common in those without MS. Although women with MS had a more unfavorable cardiometabolic profile in terms of anthropometry, BP, lipid profile, and measures of IR, AMH levels did not differ from those without MS (11.39 ± 5.31 vs 11.56 ± 5.64 ng/mL, P = 0.861).

Table 3:
Clinicometabolic profile of PCOS women with and without metabolic syndrome

AMH concentrations were comparable between obese and lean PCOS, as also between those with and without IR (data not shown in table).


The main findings of this study are that AMH do not correlate with any component of MS. Serum AMH concentrations do not differ between those with or without MS despite differences in the clinicometabolic profile.

Because menopause has been associated with a depleted follicular pool as well as worsening of cardiometabolic status, there has been growing interest to investigate whether markers of ovarian reserve like AMH might predict cardiovascular health. Serum AMH concentrations are higher in South Asian women than in other ethnicities.[28] Given the higher risk of CAD and MS in South Asians compared to the Western counterparts, it is intriguing to investigate how these higher AMH levels impact cardiovascular risk in a vulnerable population like PCOS women who, as such, present with an altered metabolic profile. Although the longitudinal impact of the high prevalence of conventional cardiovascular risk factors on coronary morbidity and mortality in PCOS is not known precisely, appropriate risk triage in reproductive age women with PCOS is advisable. Feldman et al.[26] have concluded that in women with PCOS, low AMH levels predict a greater risk of MS as a single unit decrease in AMH was associated with an 11% increase in odds of MS, indicating an independent role for AMH in cardiovascular risk stratification in these women. Jun et al.[29] also propounded that AMH is a potential cardiometabolic risk factor as low levels are related to higher HOMA-IR values and TG levels, and lower HDL-C levels. Conversely, Lin YH et al.[17] did not find significant differences in glucose tolerance, IR, lipid profile or risk of MS among the low (<4 ng/mL), moderate (4–11 ng/mL), and high (>11 ng/mL) AMH groups. In line with the latter findings, we too did not find any association between AMH levels and MS as evident from lack of correlation between AMH and various components of MS as well as from comparable AMH levels between MS and non-MS groups. There is also evidence that in PCOS, high AMH levels increase the risk for IR but not MS.[30] Some authors have observed that the association between AMH and some cardiometabolic risk factors is abolished or attenuated after controlling for potential confounders like age and BMI.[20222431] This implies that obesity may mediate the relationship between AMH and MS, and AMH may not be a significant and independent predictor of MS or future CAD risk. This is further supported from an inverse association between AMH and markers of obesity reported in most studies,[1517202223242631] which is probably due to a toxic suppressive effect of obesity on granulosa cell function and follicular AMH production, or due to a dilutional effect on serum AMH concentrations.[31] Conversely, some studies, including ours, have found no association between AMH and obesity.[11141618192125] In addition, we found no differences in AMH levels between obese and nonobese PCOS women. It is postulated that any impact of BMI on AMH in young women is probably weak as the association was found in normal weight PCOS but not in overweight or all PCOS subjects and weight reduction did not decrease AMH levels despite improvement in reproductive function.[1824] All these observations suggest that the variance of serum AMH in PCOS may not primarily be due to metabolic factors like BMI. Consequently, serum AMH may have a minor role in influencing risk of MS, which is mainly characterized by obesity. Additionally, in clinical practice, it is not useful to establish different thresholds of AMH according to BMI.

As regard BP, we did not find a statistically significant negative correlation with AMH levels, similar to few.[23] In contrast, Feldman observed a negative correlation which was, however, attenuated after adjusting for BMI.[26] This indicates that low AMH may not worsen cardiometabolic risk in PCOS as significantly or independently as obesity.

The association between AMH and lipid profile is inconsistent as well as differential with various lipid parameters in different studies.[1718192022262931] Few have found a positive correlation with total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) even after controlling for age, BMI, and androgen levels postulating that in women with PCOS, AMH has an independent association with adverse lipid profile.[1831] Increased AMH levels may lead to increased androgens which in turn may contribute to atherogenic dyslipidemia. However, despite a positive correlation between AMH and testosterone levels in our study, we did not observe any correlation between AMH and lipid profile parameters, partly in concordance with few.[1819202226] This suggests that hyperlipidemia in PCOS is independent of androgens and pathways for elevations are different for different lipid parameters.[31]

The relationship between indices of IR and AMH has been a source of controversy. Some have found a positive correlation between AMH and fasting glucose, fasting insulin, and HOMA-IR.[14151830] This is further supported by reduction in insulin and AMH levels after treatment with insulin sensitizers.[1232] This positive association may reflect indirect regulation through androgens as hyperinsulinemia leads to hyperandrogenism in PCOS which in turn causes a derangement in folliculogenesis, thus contributing to the PCOM and a higher than normal AMH levels.[2132] Conversely, some have found improvement in IR parameters, but not AMH levels, with metformin use,[33] thus adding credence to the fact that AMH levels are not associated with IR. In our study also, AMH levels were not correlated with measures of IR, similar to most studies.[1114151617192021222325] Nonetheless, a negative correlation has also been reported in literature attributable to the oxidative stress on ovarian granulosa cell function caused by IR.[1724262931]

Compared to PCOS women without MS, those with MS had a more adverse cardiometabolic risk profile in terms of measures of obesity, dyslipidemia, and IR, but AMH levels did not differ, in agreement with few reports.[30] Additionally, AMH levels were comparable between those with and without IR and obesity, which conforms to certain studies.[11181925] It is not surprising that an association between AMH and several adverse cardiometabolic parameters like HOMA-IR, WC, BMI, androgens, TC, and LDL-C has been found to be restricted only to obese PCOS cohort, thus hinting that the relationship between low AMH levels and cardiovascular risk is entirely explained by the strong inverse association between AMH and BMI.[202531] This means that early identification and treatment of obesity, IR, and MS in all PCOS women is priority to prevent future adverse cardiovascular events rather than triaging them based on AMH values as AMH levels do not directly influence the risk of these metabolic disorders.

Our study has some limitations, the main being the absence of an age and BMI-matched non-PCOS control group. The subjects evaluated in the present study were recruited from a tertiary care hospital on outpatient basis and do not reflect the true distribution of the general population. It is a cross-sectional study with small sample size so longitudinal changes in the relationship between AMH and cardiometabolic parameters cannot be assessed. Results cannot be applied to adolescent or perimenopausal PCOS as we studied women between 20 and 40 years. Number of participants aged 30 years and above was small, which may have obscured the relationship between AMH and conventional cardiometabolic risk factors, which tend to increase with advancing age. The discrepancies in the available evidence regarding the association between AMH and cardiometabolic risk factors could be due to considerable differences in geographical, ethnic, and anthropometric characteristics of study population, PCOS diagnostic criteria, study design and sample size, cutoffs used for defining MS, test assays, etc.


There is no correlation between AMH and components of MS in PCOS. AMH levels are comparable in those with and without MS, obesity, and IR. Therefore, serum AMH concentrations may not be useful as a predictor for cardiovascular risk, IR, or MS. Longitudinal cohort studies of large sample size and long-term follow-up are needed to investigate the nature, mechanisms, and direction of the complex relationship between AMH and cardiometabolic risk factors as reproductive age women with PCOS transition to menopause.

Financial support and sponsorship

Grant received from, All India Institute Of Medical Sciences, Bhubaneswar, India, as an intramural faculty project.

Conflicts of interest

There are no conflicts of interest.


Sincere acknowledgement to Mrs Jayalaxmi Sahoo, Dr Jasmina Begum, Dr Abhipsa Rath, Dr Pallabi Nayak, and Dr Deepa Sethi for providing the material support and technical help during the study.


1. Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome Fertil Steril 2004 81 19 25
2. Dokras A Cardiovascular disease risk in women with PCOS Steroids 2013 78 773 6
3. Wekker V, van Dammen L, Koning A, Heida KY, Painter RC, Limpens J, et al. Long-term cardiometabolic disease risk in women with PCOS: A systematic review and meta-analysis Hum Reprod Update 2020 26 942 60
4. Visser JA, de Jong FH, Laven JS, Themmen AP Anti-Mullerian hormone: A new marker for ovarian function Reproduction 2006 131 1 9
5. Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA, et al. Anti-Mullerian hormone expression pattern in the human ovary: Potential implications for initial and cyclic recruitment Mol Hum Reprod 2004 10 77 83
6. de Kat AC, Broekmans FJ, Laven JS, van der Schouw YT Anti-Müllerian hormone as a marker of ovarian reserve in relation to cardio-metabolic health: A narrative review Maturitas 2015 80 251 7
7. de Vet A, Laven JS, de Jong FH, Themmen AP, Fauser BC Anti-mullerian hormone serum levels: A putative marker for ovarian aging Fertil Steril 2002 77 357 62
8. de Kat AC, Dam V, Onland-Moret NC, Eijkemans MJ, Broekmans FJ, van der Schouw YT Unraveling the associations of age and menopause with cardiovascular risk factors in a large population-based study BMC Med 2017 15 2
9. Appt SE, Chen H, Clarkson TB, Kaplan JR Premenopausal anti-Müllerian hormone concentration is associated with subsequent atherosclerosis Menopause 2012 19 1353 9
10. Tehrani FR, Erfani H, Cheraghi L, Tohidi M, Azizi F Lipid profiles and ovarian reserve status: A longitudinal study Hum Reprod 2014 29 2522 9
11. Pigny P, Merlen E, Robert Y, Cortet-Rudelli C, Decanter C, Jonard S, et al. Elevated serum level of anti-Mullerian hormone in patients with polycystic ovary syndrome: Relationship to the ovarian follicle excess and to the follicular arrest J Clin Endocrinol Metab 2003 88 5957 62
12. Piltonen T, Morin-Papunen L, Koivunen R, Perheentupa A, Ruokonen A, Tapanainen JS Serum anti-Mullerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome Hum Reprod 2005 20 1820 6
13. Pellatt L, Hanna L, Brincat M, Galea R, Brain H, Whitehead S, et al. Granulosa cell production of anti-Mullerian hormone is increased in polycystic ovaries J Clin Endocrinol Metab 2007 92 240 5
14. Nardo LG, Yates AP, Roberts SA, Pemberton P, Laing I The relationships between AMH, androgens, insulin resistance and basal ovarian follicular status in non-obese subfertile women with and without polycystic ovary syndrome Hum Reprod 2009 24 2917 23
15. Piouka A, Farmakiotis D, Katsikis I, Macut D, Gerou S, Panidis D Anti-Mullerian hormone levels reflect severity of PCOS but are negatively influenced by obesity: Relationship with increased luteinizing hormone levels Am J Physiol Endocrinol Metab 2009 296 E238 43
16. Begawy AF, El-Mazny AN, Abou-Salem NA, El-Taweel NE Anti-Müllerian hormone in polycystic ovary syndrome and normo-ovulatory women: Correlation with clinical, hormonal and ultrasonographic parameters Middle East Fertil Soc J 2010 15 253 8
17. Lin YH, Chiu WC, Wu CH, Tzeng CR, Hsu CS, Hsu MI Anti-Müllerian hormone and polycystic ovary syndrome Fertil Steril 2011 96 230 5
18. Skalba P, Cygal A, Madej P, Dąbkowska-Huć A, Sikora J, Martirosian G, et al. Is the plasma anti-Mullerian hormone (AMH) level associated with body weight and metabolic, and hormonal disturbances in women with and without polycystic ovary syndrome? Eur J Obstet Gynecol Reprod Biol 2011 158 254 9
19. Woo HY, Kim KH, Rhee EJ, Park H, Lee MK Differences of the association of AMH with clinical and biochemical characteristics between women with and without PCOS Endocr J 2012 59 781 90
20. Hwang Y, Sung NY, Koo HS, Cha SH, Park CW, Kim JY, et al. Can high serum anti-Müllerian hormone levels predict the phenotypes of polycystic ovary syndrome (PCOS) and metabolic disturbances in PCOS patients? Clin Exp Reprod Med 2013 40 135 40
21. Cassar S, Teede HJ, Moran LJ, Joham AE, Harrison CL, Strauss BJ, et al. Polycystic ovary syndrome and anti-Müllerian hormone: Role of insulin resistance, androgens, obesity and gonadotrophins Clin Endocrinol (Oxf) 2014 81 899 906
22. Cui Y, Shi Y, Cui L, Han T, Gao X, Chen ZJ Age-specific serum anti-Mullerian hormone levels in women with and without polycystic ovary syndrome Fertil Steril 2014 102 230 6
23. Matsuzaki T, Munkhzaya M, Iwasa T, Tungalagsuvd A, Yano K, Mayila Y, et al. Relationship between serum anti-Mullerian hormone and clinical parameters in polycystic ovary syndrome Endocr J 2017 64 531 41
24. Lefebvre T, Dumont A, Pigny P, Dewailly D Effect of obesity and its related metabolic factors on serum anti-Mullerian hormone concentrations in women with and without polycystic ovaries Reprod Biomed Online 2017 35 325 30
25. Sahmay S, Aydogan Mathyk B, Sofiyeva N, Atakul N, Azemi A, Erel T Serum AMH levels and insulin resistance in women with PCOS Eur J Obstet Gynecol Reprod Biol 2018 224 159 64
26. Feldman RA, O'Neill K, Butts SF, Dokras A Anti-Müllerian hormone levels and cardiometabolic risk in young women with polycystic ovary syndrome Fertil Steril 2017 107 276 81
27. Misra A, Chowbey P, Makkar BM, Vikram NK, Wasir JS, Chadha D, et al. Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management J Assoc Physicians India 2009 57 163 70
28. Bhide P, Gudi A, Shah A, Homburg R Serum antimullerian hormone levels across different ethnic groups: A crosssectional study BJOG 2015 122 16259
29. Jun TJ, Jelani AM, Omar J, Rahim RA, Yaacob NM Serum anti-Mullerian hormone in polycystic ovary syndrome and its relationship with insulin resistance, lipid profile and adiponectin Indian J Endocrinol Metab 2020 24 191 5
30. Le MT, Nguyen VQ, Truong QV, Le DD, Le VN, Cao NT Metabolic syndrome and insulin resistance syndrome among infertile women with polycystic ovary syndrome: A cross-sectional study from central Vietnam Endocrinol Metab (Seoul) 2018 33 447 58
31. Rios JS, Greenwood EA, Pavone ME, Cedars MI, Legro RS, Diamond MP, et al. Associations between anti-Mullerian hormone and cardiometabolic health in reproductive age women are explained by body mass index J Clin Endocrinol Metab 2020 105 e555 63
32. Chhabra N, Malik S Effect of insulin sensitizers on raised serum anti-Mullerian hormone levels in infertile women with polycystic ovarian syndrome J Hum Reprod Sci 2018 11 348 52
33. Bayrak A, Terbell H, Urwitz-Lane R, Mor E, Stanczyk FZ, Paulson RJ Acute effects of metformin therapy include improvement of insulin resistance and ovarian morphology Fertil Steril 2007 87 870 5

Anti-Mullerian hormone; metabolic syndrome; polycystic ovary syndrome

Copyright: © 2022 Indian Journal of Endocrinology and Metabolism