Document Type : Original Article
1 Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
2 Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Polycystic ovary syndrome (PCOS) is a metabolic
disorder and one of the most common endocrine
disorders in women of reproductive age, with an
incidence of 4-18% (
Anti-Mullerian hormone (AMH) is a glycoprotein
from the family of transforming growth factor-beta
(TGF-β), secreted by granulosa cells of the antral
follicles (4-6 mm). AMH secretion gradually decreases
during follicular growth and cannot be distinguished in
follicles larger than 8 mm. Currently the serum level
of AMH, as a valid indicator of ovarian function, is
determined in women’s fertility screening and PCOS
diagnosis, allowing for targeted treatment of infertility
AMH has an inhibitory effect on the growth of
primordial follicles, thus preventing them from finishing
early in the life of a woman (
Nutritional status and obesity may affect the synthesis
of AMH, as some studies have reported a decrease in
AMH levels in obese women, indicating a negative
correlation between AMH and BMI, while others
have not mentioned a correlation between nutritional
factors, body mass index (BMI) and AMH (
In addition to energy storage, adipose tissue can
synthesize and secrete important metabolic proteins,
including adipokines that regulate multiple biological
Undoubtedly, the recognition of the factors involved in the pathogenesis of PCOS and how they interferes with the syndrome can lead to a better understanding of PCOS and therefore provides access to appropriate methods for its diagnosis and treatment. Regarding the importance of AMH, the prevalence of obesity and related dysfunction of adiponectin in PCOS, the aim of present study was to determine the correlation between AMH, adiponectin and oxidative stress markers in PCOS patients.
In this cross-sectional study, 40 PCOS patients and
40 healthy women aged 18-40 years were randomly
divided and evaluated in two groups. The sample
size was accepted by an academic static consult in
related committee. PCOS and healthy subjects were
selected by our gynecologist from her private clinic.
The diagnosis of PCOS was done based on Rotterdam
Blood samples were collected in similar conditions for
each participant on the 3rd and 5th days of their menstrual
cycle and after 8 hours of fasting. AMH Enzyme-linked
immunosorbent assay (ELISA, Beckman Coulter, USA)
was performed according to manufacturer’s instructions.
Adiponectin, gonadotropins and androgen were detected
by chemiluminescence technique (Immulite 2000,
Siemens, Germany). To evaluate IR, the HOMA-IR index
(Homeostasis Model Assessment for IR) was used as
follows: fasting blood glucose (mmol/L) concentration
x fasting insulin (μIU/mL) divided by constant 22.5; an
index > 2 indicated IR (
The TAC of the sera was assessed by Ferric reducing
antioxidant power assay (FRAP) method. Briefly, serum
(150 μl) was mixed with 1.5 ml of fresh FRAP reagent
(10 mM 2,
Griess method was used for determination of the serum
levels of NO, which includes the conversion of nitrate to
nitrite. Griess reagent facilitates the conversion of nitrite
to a deep pink azo substance (
All data were analyzed by SPSS software version 18.0 (Inc., Chicago, IL, USA) and presented as mean ± SE. Kolmogorov-Smirnov test was used to check the normality of the data. To compare the two groups, independent t test was used and Pearson correlation coefficient was used to determine the relationship between variables. The significance level was considered at P≥0.05.
In this study 80 women with a mean age of 31.36 ± 6.19
years were evaluated in two PCOS and control groups.
The subjects were similar in age in both groups. Although
the mean of BMI was higher in PCOS patients than in
the control group, this difference was not statistically
Comparison of the mean levels of AMH, Adiponectin and other hormones in control and PCOS groups. AMH; Anti-mullerian hormone, DHEA-S; Dehydroepiandrosterone sulfate, TSH; Thyroid stimulating hormone, FSH; Follicle-stimulating hormone, LH; Luteinizing hormone, and PCOS; Polycystic ovary syndrome. *; Significant difference between groups (P<0.05).
Comparison of the mean levels of AMH, Adiponectin and other factors between control and PCOS groups
|Age (Y)||32.02 ± 6.24||30.70 ± 6.14||0.341|
|BMI (Kg/m²)||25.33 ± 3.15||26.66 ± 4.24||0.117|
|AMH (ng/mL)||2.54 ± 2.44||5.16 ± 5.30||0.007|
|Adiponectin (µg/L)||30.57 ± 14.23||24.55 ± 9.41||0.029|
|DHEA-S (µg/mL)||85.25 ± 47.58||119.78±60.31||0.006|
|Testosterone (nmol/L)||0.76 ± 0.13||0.92 ± 0.29||0.002|
|Prolactin (ng/mL)||15.62 ± 6.66||17.57 ± 8.59||0.259|
|TSH (µIU/mL)||2.70 ± 1.32||2.96 ± 1.12||0.354|
|FSH (mIU/mL)||8.60 ± 4.79||7.04 ± 3.19||0.090|
|LH (mIU/mL)||5.97 ± 2.93||6.50 ± 3.65||0.476|
|FBG (mg/mL)||86.96 ± 9.52||85.63 ± 7.53||0.488|
|Insulin (µIU/mL)||5.68 ± 3.48||8.66 ± 3.98||0.001|
|IR-HOMA||1.25 ± 0.87||1.86 ± 0.90||0.003|
|TAC (µmol)||260.02 ± 212.71||231.26 ± 178.51||0.517|
|NO (µmol)||26.01 ± 12.41||31.11 ± 14.54||0.213|
Data are presented as mean ± SD.
AMH; Anti-mullerian hormone, PCOS; Polycystic ovary syndrome, BMI; Body mass index, DHEA-S; Dehydroepiandrosterone sulfate, TSH; Thyroid stimulating hormone, FSH; Follicle-stimulating hormone, LH; Luteinizing hormone, FBG; Fasting blood glucose, IR-HOMA; Insulin resistance- homeostatic model assessment, TAC; Total antioxidant capacity, NO; Nitric oxide, and *; Independent Sample t test.
AMH level in PCOS group was significantly
higher than in the normal group (5.16 ± 5.30 vs.
2.44 ± 2.49) (P=0.007). Also, there was a significant
difference in the adiponectin level between the two
groups (P=0.029), as it was lower in the PCOS
group compared to the control group (24.55 ± 9.41
vs. 30.57 ± 14.23) (
The mean of fasting blood glucose (FBG) was not
significantly different between the two groups, but the
mean of insulin in the PCOS group was significantly
higher than in the control group (P=0.001). Also, the
mean of insulin resistance-homeostatic model assessment
(IR-HOMA) was significantly different between the two
groups (P=0.003), It was higher in the PCOS group than
control group (
In the PCOS group, there was a significant negative correlation between age and AMH (P=0.002, r=-0.46), age and dehydroepiandrosterone sulfate (DHEA-S, P=0.045, r=-0.32), body mass index (BMI) and FSH (P=0.03, r=-0.34), and adiponectin and testosterone (P=0.02, r=-0.36). Also, There was a significant positive correlation between BMI and insulin (P=0.04, r=0.32) and IR (P=0.04, r=0.32), AMH and LH (P=0.10, r=0.4), DHEA-S and testosterone (P=0.003, r=0.45), DHEA-S and TAC (P=0.005, r=0.43), prolactin and nitric oxide (NO, P=0.04, r=0.42), and TSH and TAC (P=0.005, r=0.43). FBG (P=0.000, r=0.59) and insulin (P=0.000, r=0.99) also had a significant positive correlation with the IR index (IR-HOMA).
Comparison of insulin resistance index, TAC and NO in in control and PCOS groups.
FBG; Fasting blood glucose, IR-HOMA; Insulin resistance-homeostatic model assessment, TAC; Total antioxidant capacity, NO; Nitric oxide, and PCOS; Polycystic ovary syndrome.*; Significant difference between groups (P<0.05.)
In control subjects, there was a significant negative correlation between Age and AMH (P=0.000, r=- 0.76), Age and testosterone (P=0.01, r=-0.39), AMH and adiponectin (P=0.03, r=-0.35), and AMH and FSH (P=0.005, r=-0.43). There was a significant positive correlation between age and FSH (P=0.037, r=0.33). AMH and testosterone (P=0.01, r=0.39), prolactin and TAC (P=0.002, r=0.48), FBG and insulin (P=0.004, r=0.45), FBG and IR-HOMA (P=0.000, r=0.61), insulin and IR-HOMA (P=0.000, r=0.98), and IR-HOMA and NO (P=0.45, r =0.44). In the control subjects, increasing in BMI leads to decreasing in adiponectin (P=0.001, r=- 0.5) and DHEA-S (P=0.04, r=-0.34).
Several factors were studied in this study, but the most important results were the significant differences between AMH, adiponectin, androgens and IR between the two groups of PCOS patients and healthy controls. We observed significant correlations between these variables in the two groups independently. PCOS group showed biochemical features associated with PCOS, such as higher levels of androgens, insulin and IR. Also, there was a higher AMH and lower adiponectin level in PCOS patients. The most important correlation found in the PCOS group was a significant positive correlation between AMH and each of the factors LH, DHEA-S, TAC, prolactin, NO, BMI, insulin and IR. In addition, there was a significant negative correlation between AMH and DHEA-S, BMI and FSH, adiponectin and testosterone in the PCOS group. However, in the control group, there was a significant positive correlation between age and FSH, AMH and testosterone, prolactin and TAC, FBG and insulin, and IR and NO. On the other hand, there was a significant negative correlation between age and AMH, age and testosterone, BMI and adiponectin, BMI and DHEA-S, AMH and adiponectin, and AMH and FSH in this group.
The results of our study, similar to OlszaneckaGlinianowicz et al. (
Adiponectin plays an important role in anti-inflammatory
processes, insulin sensitivity and obesity. The results of
some studies (
In recent years, AMH has been used as a key factor
for evaluating ovarian function and an indicator for
determining the number of ovarian follicles and reverse.
Due to the increase in the number of small follicles in the
ovaries of PCOS patients, the increase of this hormone
is not unexpected. In our study, after adjustment for
age, AMH was significantly higher in the PCOS group,
which was similar to the results of Woo et al. (
In some studies, the mean of FSH in patients with
PCOS was higher than in the control group (
There was a significant positive correlation between
AMH and LH in the PCOS group and a significant
negative correlation between AMH and FSH in the
control group in the present study. In both groups the
mean of AMH decreased with aging, which was similar to
other previous studies (
Although some studies have reported a negative
correlation between AMH and BMI (
In the present study, the correlation between AMH
and adiponectin was negative in both groups, but it was
significant only in the control group. In the study of Woo
et al. (
Regarding prolactin, there is a hypothesis that
polycystic ovaries affect the activity of dopamine in the
hypothalamus and cause hyperprolactinemia in these
The correlations between variables in the present study and the significant differences between the two groups can indicate the role of these factors in the pathogenesis of PCOS, which is a multifactorial disorder. More in depth research is needed for a better understanding of the molecular mechanism, cellular changes and gene expression that initiate PCOS pathogenesis.
Adiponectin changes can lead to impaired ovarian function and ovarian hormones in the reproductive age and its deficiency in PCOS patients may be associated with IR and increased insulin levels. Insulin is one of the effective factors in increasing the number of antral follicles and ultimately increasing ovarian volume. In women suffering from PCOS hyperinsulinemia may increase AMH levels. So it can be concluded that the role of adiponectin in increasing insulin sensitivity plays a key role in controlling the synthesis of AMH in women of reproductive age.