Evaluation of Role of Some Adipokines and Anti-Mullerian Hormone in Women with Polycystic Ovary Syndrome in Nineveh Governorate – Iraq

Not all women diagnosed with PCOS share the same cardiovascular risk profiles

During the last years, anti-Mullerian hormone (AMH) has been transformed into a “hot issue” of Reproductive Medicine, as it has attracted the attention of many research groups and has found considerable clinical applications. In this review, we have summarized available evidence on possible roles of AMH in women with polycystic ovary syndrome (PCOS). We have arranged the material into three sections. In the first section, we briefly present the AMH as a molecule, in the second we pay special attention on AMH involvement in PCOS pathophysiology and, in the third ­section, we discuss possible roles of AMH as a predictive factor in women with PCOS undergoing assisted reproduction technologies (ART). Serum AMH concentrations, being stable and consistent throughout the menstrual cycle, constitute a reliable marker of ovarian reserve; thus, AMH has already found a role in the clinical practice, particularly when combined with classic markers of ovarian reserve such as age, follicle-stimulating hormone (FSH), and antral follicle count (AFC). The significance of AMH in women with PCOS undergoing ART is increasing as well. On top of being a marker of ovarian reserve, AMH has been used for predicting success of ovulation induction and controlled ovarian hyperstimulation protocols, as well as avoidance of ovarian hyperstimulation syndrome (OHSS). Despite this evidence, many issues remain to be elucidated. AMH physiology is still obscure, especially its exact role in ovarian folliculogenesis, significance of serum and follicular fluid concentrations, and ­possible extraovarian actions. As far as PCOS is concerned, there is agreement that AMH concentrations are elevated in women with the syndrome as compared to normo-ovulatory women. Nevertheless, it is still not known if this difference is the result of disrupted folliculogenesis, due to increased number of small antral follicles, or the cause of it, due to AMH inhibition on folliculogenesis. Data on AMH pathophysiology in adolescent girls with PCOS are particularly scarce. The answers to these questions will broaden the spectrum of AMH clinical applications. Adjustment of overall ART strategy and individualization of protocols according to AMH concentrations seems to constitute possibilities for the near future. More distant applications could include use of AMH in hormonal contraception, given its inhibitory action on ­follicular development, or even development of AMH-antagonists in the therapeutic approach of women with PCOS.

Background The objective was to study ovarian reserve values in women of early reproductive age with polycystic ovary syndrome (PCOS) according to their phenotype. Materials and methods Two hundred women of early reproductive age with PCOS and without PCOS were studied by clinical, laboratory (hormonal), ultrasound and statistical methods. Results The anti-Müllerian hormone (AMH) index in women with PCOS with the main (A) and non-androgenic (D) phenotypes corresponded to a high level, with anovulatory (B), ovulatory (C) corresponding to a normal level. AMH in women with the main (A) phenotype differed and was higher compared with women with anovulatory (B) and ovulatory (C) phenotypes and had no differences to women with the non-androgenic (D) phenotype. No differences in the AMH level between anovulatory (B) and ovulatory (C) phenotypes have been established. Ultrasound parameters of the ovaries (volume, number of antral follicles in the section, average diameter of the follicles) of women with PCOS of the main (A), ovulatory (C) and non-androgenic (D) phenotypes were statistically significantly larger than healthy ones. With anovulatory (B) phenotype these figures did not differ from the control group. When comparing phenotypes by ultrasound parameters of the ovaries the main (A), ovulatory (C) and non-androgenic (D) phenotypes did not have any differences among themselves. Anovulatory phenotype (B) had lower ultrasound indices. Conclusion The study of indicators of ovarian reserve in women of early reproductive age with PCOS is a promising direction that will allow to more accurately determine the reproductive potential of each particular woman and influence the choice of treatment tactics.

A variant in the fibrillin-3 gene is associated with TGF-β and inhibin B levels in women with polycystic ovary syndrome

Reproductive dysfunctions of polycystic ovary syndrome (PCOS) and blood anti-mullerian hormone (AMH) concentration are significantly influenced by the dietary advanced glycation end products (AGEs). The interplay between AGEs and their soluble form of receptor, might exert a protective role on the follicular environment and affect AMH concentration. This study investigated the relationship between soluble receptor for advanced glycation end-products (sRAGE) levels in follicular fluid (FF) and serum AMH levels in PCOS and non-PCOS women. Among 43 women of reproductive age who participated in this case-control study 26 non- PCOS women were assigned to the control group, while 17 participants were diagnosed with PCOS and allocated to the case group. Prior to the in vitro fertilization (IVF) procedure, fluid samples were collected and levels of FF sRAGEs and serum AMH were recorded through the use of commercially available ELISA kits. Correlation analysis, without age adjusting, revealed a statistically considerable and positive association between FF sRAGE and serum AMH concentration in PCOS women (P=0.012, r=0.596). Moreover, after age stratification, the same pattern was observed in some age groups; in PCOS women aged 40 years or older (r=1, P<0.001), as well as those younger than 30 years (r=0.922, P=0.003), correlation analysis demonstrated a significant and positive relationship between FF sRAGE and serum AMH levels. The association between sRAGE and AMH in women with PCOS is primarily affected by their age, whereas non-PCOS women showed no relationship. The results show that the levels of these receptors (sRAGE) show their specific effects in young women and women over 40 years old and not in middle age and target the ovarian reserve. It seems to act as a defensive shield in older women and increase fertility in young women.

Polycystic ovary syndrome, an enigmatic syndrome begging for a name change

To explore the relationship of insulin resistance (IR) and adipokines (leptin, adiponectin, RBP4) to anti-Mullerian hormone (AMH) levels in women without polycystic ovary syndrome (PCOS). We recruited 120 healthy, reproductive age women without PCOS. An overnight fasting blood draw, anthropometric measurements, analyses of serum levels of AMH, adipokines (leptin, adiponectin and RBP4) and total testosterone, a homeostasis model assessment for insulin resistance (HOMA-IR) and a transvaginal ultrasound scan were performed between the third and fifth day of their spontaneous menstrual cycles. Higher HOMA-IR levels were associated with lower levels of AMH. After adjustment for age, serum AMH levels negatively correlated with insulin, fasting glucose, HOMA-IR and RBP4. However, a positive correlation was identified between serum AMH and adiponectin. A final multiple stepwise linear regression demonstrated that HOMA-IR was independently associated with AMH. An independent relationship exists between HOMA-IR and AMH in women without PCOS, possibly due to the effect of abnormal insulin action on AMH secretion by granulosa cells.

Study question To develop an age-specific percentile distribution of anti-Müllerian hormone (AMH) in patients with polycystic ovary syndrome (PCOS) measured by three different assays. Summary answer Our age-related normograms may help to interpret AMH levels in PCOS patients and facilitate the use of AMH as a diagnostic tool across age ranges. What is known already In the last years, AMH assessment has gained widespread use in the clinical settings of several conditions. However, several challenges still exist to adopt the AMH as a marker of polycystic ovary morphology (PCOM), as included in the recently updated international guideline. Although different evaluations of age- and assay-specific reference ranges have been published in the last years, these studies have mainly been conducted in normo-ovulatory or infertile women and little is known about the higher range of AMH levels, especially in women with PCOS. Study design, size, duration Retrospective single-center cross-sectional study, including 2,725 women with PCOS who consulted the Reproductive Endocrinology and Infertility Clinic of the Erasmus University Medical Center, Rotterdam, The Netherlands. Participants/materials, setting, methods A total of 2,725 women aged 20 to 40 years with PCOS were included. PCOS was diagnosed according to the Rotterdam Criteria. Serum AMH levels were measured using the following AMH assays: (1) Gen II AMH ELISA, 2) picoAMH assay, and 3) Elecsys AMH plus assay. Age-specific centile curves were constructed using the LMS method. The correlations between AMH with clinical, endocrine, and ultrasound features were also evaluated. Main results and the role of chance To our knowledge, this is the first study with real-world data reporting AMH age-specific percentile nomograms in a large population of PCOS women using three different assays. The 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles were calculated according to a population/based approach per age (years) for the Gen II, the picoAMH, and the Elecsys assays. We also considered the age-percentile values of AMH in PCOS patients for the Gen II, the picoAMH and the Elecsys assays according to the cut-offs previously proposed in literature for each specific assay. Interestingly, in our population, a high percentage of women with polycystic ovarian morphology (PCOM) showed AMH levels lower than the cut-offs proposed. Serum AMH levels were significantly higher in patients with phenotype A compared to all other phenotypes for all three assays. For all three assays, we found a statistically significant positive correlation between AMH levels and LH, LH/FSH ratio, testosterone, androstenedione, FAI, mean follicular number, and mean ovarian volume. In contrast, AMH levels were negatively correlated with BMI in all groups. Limitations, reasons for caution This is a retrospective cross-sectional study. Longitudinal studies with a large cohort of women that could be followed for many years are needed to validate our nomogram. Wider implications of the findings AMH threshold levels can be influenced by several variables, making it difficult to identify a general cut-off to diagnose PCOM. Further research should overcome the concept of a single cut-off value. The results of the present study may help clinicians interpret AMH levels in PCOS patients across age ranges. Trial registration number In this retrospective cross-sectional study, 2,725 women who consulted the Reproductive Endocrinology and Infertility Clinic of the Erasmus University Medical Center, Rotterdam, The Netherlands, were included. The Medical Ethical Review Board of the Erasmus University Medical Center Rotterdam approved retrospective studies within this patient population, which includes women with ovulatory dysfunction (MEC-2020-0534).

The reproducibility of serum anti-Müllerian hormone in subfertile women: within and between patient variability

Introduction: Polycystic Ovary Syndrome (PCOS) is the most prevalent endocrine condition in women, affecting 5 – 10% of women who are of reproductive age. Together with other Rotterdam criteria, elevated blood AMH levels are considered a significant diagnostic for PCOS and may be used as a powerful predictor to reflect the certainty of the diagnosis of PCOS in women of reproductive age. Objective: This study aims to prove high AMH as a predictor for PCOS.Methods: This study is an analytic study with a case-control study design. A total of 30 respondents were divided into PCOS and control groups. All women were subjected to anthropometric assessments such as measurement of height, weight, BMI, and trans-abdominal ultrasonography for ovaries. Data analysis was carried out using independent t-tests and Chi-Square tests.Result: The data analysis revealed that the PCOS group’s mean AMH levels were considerably different (p&lt;0.05), with 6.5±1.75 greater than the control group’s 3.34±0.64. AMH levels were found to be twice as high in the PCOS group as in the control group. AMH levels and PCOS incidence were compared using the Chi-Square test; the odd ratio is 17.875 (95% CI = 2.73 -116.8; p=0.001).Conclusion: High levels of AMH at reproductive age can 18 times predict the risk of PCOS.Kadar Antimullerian Hormon (AMH) Tinggi sebagai Prediksi Sindrom Polikistik Ovarium pada Wanita Usia Reproduksi di RSUD Giri EmasAbstrakPendahuluan: Sindrom Ovarium Polikistik (SOPK) merupakan kelainan endokrin yang menyerang kira-kira 5 - 10% wanita usia subur dan dianggap sebagai kelainan endokrin yang paling umum pada wanita. Kadar AMH serum yang meningkat saat ini dianggap sebagai penanda penting untuk SOPK dan dapat digunakan sebagai prediktor kuat untuk mencerminkan kepastian diagnosis SOPK pada wanita usia subur bersama dengan kriteria Rotterdam lainnya. Tujuan: Penelitian ini bertujuan untuk membuktikan kadar AMH yang tinggi sebagai prediktor SOPK. Metode: Penelitian ini merupakan penelitian analitik dengan desain studi kasus kontrol. Sebanyak 30 responden akan dibagi menjadi kelompok SOPK dan kelompok kontrol. Semua wanita menjalani penilaian antropometri seperti pengukuran tinggi badan, berat badan, BMI, dan ultrasonografi trans-abdominal untuk ovarium. Analisis data dilakukan dengan uji t independen dan uji Chi-Square. Hasil: Analisis data menunjukkan rerata kadar AMH pada kelompok SOPK lebih tinggi 6,5±1,75 dibandingkan dengan kontrol 3,34±0,64 dan berbeda bermakna (p&lt;0,05). Ditemukan kadar AMH pada kelompok SOPK dua kali lebih tinggi dibandingkan dengan kontrol. Untuk mengetahui hubungan kadar AMH dengan kejadian PCOS digunakan uji Chi-Square dan odd ratio menunjukkan 17,875 (95% CI = 2,73 -116,8 ; p=0,001).Kesimpulan: Dapat disimpulkan bahwa pada penelitian ini kadar AMH yang tinggi pada usia reproduksi dapat memprediksi risiko PCOS sebesar 18 kaliKata kunci: AMH, PCOS, oligomenorea, hiperandrogen, anovulasi

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women, affecting 5%-10% worldwide. It is a multisystem condition characterized by hyperandrogenism, chronic anovulation, and polycystic ovaries, with potential long-term complications including type 2 diabetes, cardiovascular disease, and metabolic syndrome. This study compares serum anti-Müllerian hormone (AMH) levels between women with and without PCOS and evaluate the prevalence of glucose intolerance and metabolic syndrome in these groups. This prospective comparative study was conducted on 150 women of reproductive age attending the gynecology outpatient department at Rajarajeshwari Medical College and Hospital, Bengaluru. Group A (n = 75) included women without PCOS, and Group B (n = 75) included women diagnosed with PCOS based on the Rotterdam criteria (2003). Clinical examinations, serum AMH levels, 75 g oral glucose tolerance test, lipid profile, blood pressure, body mass index, waist circumference, and waist-hip ratio were assessed. Data were analyzed to determine associations between AMH, glucose intolerance, and metabolic syndrome. Serum AMH levels were significantly higher in the PCOS group (mean 7.98 ng/mL), with 63% showing elevated AMH (P < 0.005). Metabolic syndrome was also significantly more common in women with PCOS (P < 0.005). Glucose intolerance was observed in 25% of women with PCOS, but no significant association was observed between serum AMH levels and glucose intolerance in women with PCOS. Serum AMH is significantly elevated in women with PCOS and is as a potential marker for predicting metabolic risk but has no association with glucose intolerance in PCOS patients.

Objectives: This study aimed to investigate the effect of resistance training in water and land with vitamin D on anti-Mullerian hormone in women with polycystic ovary syndrome (PCOS). Methods: Sixty women with PCOS (20 - 35 years old) referred to the Hafez Hospital in Shiraz in 2018 were selected and randomly divided into six groups of (1) control, (2) water training, (3) land training, (4) vitamin D, (5) water training with vitamin D, and (6) land training with vitamin D. Groups 2, 3, 5, and 6 performed resistance training in water and land for eight weeks, three sessions per week, while groups 4, 5 and 6 consumed vitamin D for eight weeks. For statistical analysis of data independent samples t-test, one-way ANOVA and Tukey’s post hoc tests were used (P ≤ 0.05). Results: Training in water and land have no significant effect on anti-Mullerian hormone (P ≥ 0.05); vitamin D, training in water with vitamin D, and training in land with vitamin D have significant effect on reduction of anti-Mullerian hormone (P = 0.001); training in water with vitamin D and training in land with vitamin D have more effect on reduction of anti-Mullerian hormone rather than vitamin D (P ≤ 0.05) and after training in water with vitamin D (P = 0.01) and training in land with vitamin D (P = 0.001) there is a significant relationship between anti-Mullerian hormone changes and weight. Conclusions: It appears that resistance training in water and land combined with vitamin D consumption may decrease the anti-Mullerian hormone by reduction in weight and as a result improve ovarian and reproductive function in women with PCOS.

Polycystic ovary syndrome (PCOS) is an anovulatory disorder characterized by excess androgen production and increased LH secretion. Serum anti-Mullerian hormone (AMH) is also elevated in this disorder. Women with PCOS exhibit a positive correlation between AMH and LH levels and recent in vitro data demonstrate that LH can directly stimulate AMH production by granulosa cells from women with PCOS. The objective of the study was to directly test whether LH increases AMH production in women with PCOS in vivo by assessing responses after recombinant human chorionic gonadotropin (r-hCG) stimulation. This was a prospective study. The study was conducted at a research center at an academic medical center. Women with PCOS (n = 28) and normal controls (n = 29) participated in the study. Blood samples were obtained before and 24 hours after iv administration of 25 μg r-hCG. Basal and stimulated serum AMH, androstenedione, T, and 17-hydroxyprogesterone levels were measured. Baseline AMH levels in women with PCOS were greater than in normal controls and correlated with levels of LH as well as androstenedione, T, and 17-hydroxyprogesterone. A rise of serum AMH levels was not observed after r-hCG administration in women with PCOS or normal ovaries. These findings are in contrast to in vitro evidence demonstrating that AMH secretion by granulosa cells of PCOS women in response to LH stimulation and suggest AMH regulation in vivo is complex and that the elevated serum AMH in women with PCOS is not a direct effect of the excess LH production characteristic of PCOS.

The objectives of this study were: (1) to determine anti-Mullerian hormone (AMH) levels in menopausal women, and (2) to confirm the source of AMH in cycling women and its disappearance after the removal of the source. An observational and prospective study was conducted. A total of 47 women were recruited for the study. The study population consisted of the following groups of patients: (A) women of late reproductive age (n = 24; mean age +/- SD, 44 +/- 2.8 years); (B) menopausal women (n =14; mean age, 56 +/- 4 years); and (C) regularly cycling women undergoing surgical menopause (n = 9; mean age, 43 +/- 4 years). Blood samples were obtained from all patients. In patients undergoing surgery, blood samples were obtained before and after surgery. AMH was undetectable in 13 of 14 postmenopausal women, whereas it was undetectable in only two of 24 women of late reproductive age. A significant negative correlation has been found between AMH and age or follicle-stimulating hormone (FSH) in women of late reproductive age. In women who were candidates for oophorectomy, samples were obtained 3-5 days after surgery. AMH was undetectable after the surgery in all women. We found that AMH levels decreased in women in the late reproductive period and that menopause and ovariectomy in regularly cycling women are associated to undetectable AMH in serum. These observations confirm that the ovary could be the only source of AMH in women and that it is a novel marker for ovarian aging.

Anti-Müllerian hormone (AMH) is largely expressed throughout folliculogenesis and its levels may represent both the quantity and quality of ovarian follicle pool. We conducted this study to evaluate the levels of AMH in women with polycystic ovarian syndrome (PCOS) before and after metformin therapy. 22 consecutive patients with PCOS and 20 healthy age-matched controls were investigated. The patients received 2 550 mg/day metformin for 6 months. Serum levels of AMH, sex hormones, insulin, blood glucose, and lipids were measured before and after metformin therapy. The basal AMH levels in patients with PCOS (42.34±6.42 pmol/l) were significantly elevated in comparison with the controls (21.58±3.41 pmol/l), p=0.008. 17 patients completed 6 months therapy with metformin. Of them, 13 responded clinically by restoration of regular menstrual cycles. The AMH levels of these 13 women decreased from 45.67±9.30 pmol/l to 38.25±6.89 pmol/l (16.27%). In the other 4 patients who did not show satisfactory clinical response to metformin, AMH levels increased from 31.30±16.52 to 80.77±12.73 (p=0.021). The patients who responded to metformin were significantly overweight, had higher BMI, waist circumference, body fat, and blood pressure as compared to nonresponders. AMH levels are significantly elevated in women with PCOS and they may serve as a marker for evaluation of treatment efficacy with metformin. Furthermore, obese PCOS patients are more likely to respond to metformin therapy with maximal doses as compared to the ones with low body mass index.