This study aims to lay a foundation for the future exploration of ovulation and metabolic abnormalities in PCOS patients in China. We found that >50% of patients with PCOS had IR, obesity, HA, and abnormal glucose tolerance. AMH, T, and HOMA-IR levels were affected by age, and older participants had lower AMH, HOMA-IR, and androgen levels. Glycated hemoglobin levels were higher and AMH, LH/FSH, and LH levels were lower in non-obese individuals than in obese individuals. Participants in the NIR group were older than those in the IR group. AMH, LH, LH/FSH, and T levels in the IR group were significantly higher than those in the NIR group. AMH levels were positively correlated with LH, LH/FSH, T, FINS, and HOMA-IR levels as well as the FAI and negatively correlated with age, BMI, and SHBG levels. Through multiple linear regression, we found that AMH levels could be explained by T, LH/FSH, FINS, SHBG, and LH levels and BMI.
PCOS is a complex reproductive, endocrine, and metabolic disease. HA and ovulation dysfunction are the main clinical difficulties in patients with PCOS. Importantly, > 50% of patients with PCOS also suffer from additional metabolic diseases, such as IR and obesity . PCOS further aggravates the accompanying HA and ovulation disorder, severely affecting the physical and mental health of women of reproductive age. AMH is a dimeric glycoprotein synthesized by ovarian granulosa cells. Its secretion is primarily influenced by the early follicular absorption rate in the follicular cisterna. It is independent of changes in the menstrual cycle and is a reliable indicator for the clinical evaluation of ovarian reserves. AMH levels in patients with PCOS are 2–3 times higher than that of those in healthy individuals  and are consistent with the increase in the number of intracavity follicles (AFCs). Previous studies have suggested that AMH measurements could be helpful in the diagnosis and assessment of the severity of PCOS; however, serum AMH levels are affected by multiple factors, such as the environment and heredity. Therefore, understanding the influencing factors of AMH in women with PCOS is advantageous to better understand the clinical significance of AMH level fluctuations.
IR and compensatory hyperinsulinemia (HI) are some of the causes of HA and ovulation dysfunction in women with PCOS. In women with PCOS, IR was present in 50–70% of patients regardless of obesity. Researchers believe that the inability of insulin to bind to its receptor and the change in insulin signal transduction can lead to IR. IR and HI can increase the free T level by stimulating the production of ovarian androgen and inhibiting the synthesis of SHBG in the liver. Moreover, it can also increase adrenal androgen levels, thereby stimulating the production of ovarian steroids mediated by LH and preventing follicular development . In the follicular fluid of women with PCOS, the imbalance between oxygen free radicals or reactive oxygen species and antioxidant factors can lead to cell damage, which prevents oocyte maturation and decreases embryo quality. Meanwhile, the inflammatory environment caused by oxidative stress in women with PCOS promotes the occurrence of IR and HA . IR and HI can be further accompanied by a series of metabolic abnormalities, such as abnormal glucose tolerance, uric acid metabolism, dyslipidemia, hypertension, and endothelial dysfunction . IR in women with PCOS who are not pregnant and in early pregnancy not only increases the incidence of hypertension, gestational diabetes, and preeclampsia but also aggravates neonatal complications such as congenital malformations in early progeny and the long-term risk of IR, obesity, and diabetes in later progeny . IR and HA are mutually causal, which can further worsen the metabolic disorder.
Previous studies have suggested that AMH levels are positively correlated with HA and LH and significantly negatively correlated with age in patients with PCOS, which is consistent with our current results; however, the exact relationship between IR and AMH levels is unclear, and studies on the correlation between IR and AMH levels in patients with PCOS have been reported. A relevant analysis of AMH genotypes in PCOS found that there were significant differences in the distribution of AMH genotypes between women with PCOS with IR and healthy women, but there were no differences in the distribution of AMH genotypes between women with PCOS without IR and healthy women. When metformin, an insulin sensitizer, was used to treat PCOS for 2 months, the serum AMH level decreased and ovulation increased, suggesting that there is an etiological relationship between AMH levels and IR-PCOS, which may be mediated by LH and T levels. Previously, researchers believed that LH could cause a four-fold elevation in AMH production in ovarian granulosa cells of women with PCOS and elevate AMH expression with or without ovulation. Androgens can also stimulate FSH independent of follicular development and may increase AMH production . Although the internal mechanism of the relationship between AMH levels and PCOS is currently unclear, it appears that LH and androgens are related to the correlation between IR and AMH levels in PCOS. Wiweko et al.’s study also revealed that serum AMH was significantly correlated with the HOMA-IR level, and there were differences between different PCOS phenotypes . In this study, 57% of our participants presented with IR, and the AMH, LH, LH/FSH, and T levels in women with IR-PCOS were significantly higher than those in women with NIR-PCOS; however, there was no difference in BMI. We determined that FINS and HOMA-IR were significantly positively correlated with AMH levels, which suggests that PCOS is independent of obesity and IR. This also shows that there is a difference in AMH levels among patients with PCOS with or without IR, suggesting that AMH levels can indirectly reflect the severity of PCOS. Our results are consistent with those of previous studies, suggesting that AMH levels are positively correlated with IR and HI levels in patients with PCOS.
In China, 34.1–43.3% of women with PCOS are obese . The negative effects of obesity on reproductive health and fertility, such as ovulation dysfunction, infertility, abortion, and related pregnancy complications, are well documented . Notably, obesity is one of the main contributors to the development of PCOS, can inhibit the production of gonadotropin through IR and produces circulating T, and can lead to IR and HI, thereby reducing the secretion of SHBG and resulting in HA. Both obesity and IR can disrupt the development of female antral follicles, interfere with the hypothalamic-pituitary-ovary axis, and lead to chronic ovulation failure . Studies have also found that obese women with PCOS have higher infertility rates, poor response to ovulation induction drugs, poor embryo quality, a low success rate of in vitro fertilization, and significantly increased adverse pregnancy outcomes . Moreover, a recent meta-analysis demonstrated that BMI was negatively correlated with AMH . In obese women, changes in the ovarian follicular microenvironment, including steroidogenesis, metabolism, and inflammation, indirectly affect AMH levels. A decrease in AMH levels has been suggested to be the result of metabolism, storage, and clearance in obese individuals.
Piouka et al. demonstrated that the serum AMH levels of overweight and obese women with PCOS were significantly lower than those of lean women with PCOS . Previous studies on the relationship between obesity biomarkers and AMH levels in women with PCOS have also revealed conflicting reports, which can vary depending on the definition of obesity and grouping based on BMI. In this study, participants were divided into obese and non-obese groups according to the WHO standard for obesity in Asia, and we found that AMH, LH/FSH, and LH levels in the obese group were lower than those in the non-obese group. Correlation analysis of AMH also showed that there was a significant negative correlation between AMH levels and BMI, and BMI could independently affect AMH levels, supporting the concept that follicular development may be impaired in women with PCOS with increased BMI. Obese women with PCOS primarily show abdominal obesity and large waist and hip circumferences, and other records of patients with PCOS were not included in our present study; therefore, there may be some bias in the determined relationship between obesity and AMH and HOMA-IR levels.
Normal ovarian development is affected by the factors inside and outside the ovary; factors inside the ovary include growth factors, cytokines, and inhibin in the follicular fluid, and the concentration is related to the plasma level. External factors include FSH deficiency, LH hypersecretion, high androgen levels in the ovaries and adrenal gland, IR, and HI. Unbalanced development of these factors will alter ovarian development and the generation of mature oocytes, thus affecting the fertility of women with PCOS. Most women with PCOS are also afflicted by manifestations of metabolic syndrome such as obesity, hypertension, dyslipidemia, and IR. Up to 30–40% of women with PCOS have impaired glucose tolerance, and up to 10% develop type 2 diabetes before the age of 40 years . In this study, AFC was not included because of the lack of specific values after their number exceeded 12 on ultrasound, and the large number of reports on the correlation between AMH and AFC; however, as the serum AMH level reflects small follicles that cannot be observed on ultrasound, the theoretical AMH level is more accurate than the AFC level, suggesting that the AMH level may play a role in the diagnosis of PCOS. Because of the correlation between AMH levels and obesity and IR, we believe that the clinical combination of AMH and HOMA-IR levels and BMI could be used to help determine the severity of endocrine and metabolic disorders in patients with PCOS. The exact mechanism of the relationship between AMH levels and IR and obesity in PCOS needs to be further elucidated, and there is no consistent serum AMH diagnostic threshold for PCOS. Moreover, because of the lack of a control group, we did not further elaborate on the diagnostic significance of AMH levels in PCOS. These are the limitations of the study. Therefore, we hope that more preclinical and clinical studies are conducted in the future to verify the role of AMH levels in the prediction, prevention, and treatment of PCOS and to provide more of a theoretical basis for the exploration of the etiology of PCOS.