Sibutramine administration decreases serum anti-Müllerian hormone (AMH) levels in women with polycystic ovary syndrome

Objective

To investigate the effect of diet, physical exercise and sibutramine administration on serum anti-Müllerian hormone (AMH) levels, hormonal and metabolic parameters in overweight and obese patients with polycystic ovary syndrome (PCOS).

Study design

Prospective clinical study, in an outpatient clinic setting, of 76 overweight and obese women with PCOS. All patients were placed on a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) for the first month and then on either a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) or a hypocaloric diet and physical exercise for the subsequent 6 months. Serum AMH levels, body composition, hormonal and metabolic features and insulin sensitivity indices were evaluated at baseline and at 4 and 7 months of treatment.

Results

Body weight reduction was greater in the sibutramine group. Moreover, serum FSH and testosterone levels decreased, and SHBG, free androgen index and all indices of insulin resistance significantly improved at 4 and 7 months. Serum AMH levels decreased only in PCOS women who received sibutramine, at both 4 and 7 months of treatment.

Conclusion

A hypocaloric diet and a diet plus sibutramine both resulted in significant weight loss in overweight and obese women with PCOS. Patients who received sibutramine showed greater weight loss and improvement in hyperandrogenemia and insulin sensitivity after 7 months of treatment. Serum AMH levels significantly decreased at both 4 and 7 months of treatment only in PCOS women who received sibutramine, indicating a possible direct, gonadotropin independent effect of sibutramine on the ovarian production of AMH.     

Clinical significance of serum concentration of anti-Müllerian hormone in obese women with polycystic ovary syndrome

In the human ovary, expression of anti-Müllerian hormone (AMH) is detected primarily in granulosa cells of preantral and small antral follicles. The aim of this study was to compare serum AMH measurements in obese women with polycystic ovary syndrome (PCOS) with those in obese normo-ovulatory women and to evaluate the role of AMH as a predictor of ovulation induction by clomiphene citrate compared to FSH. Sixty-eight obese women with PCOS were compared to 17 normoovulatory obese women. All women had a body mass index greater than 30 kg/m(2). Women with PCOS received clomiphene citrate (150 mg/day) for 5 days starting from day 3 of cycle and were subdivided into responsive and non-responsive groups. There was a significant difference in AMH concentration between women with PCOS and the control group (P < 0.05) and also between women with PCOS who responded to clomiphene citrate and those who did not (P < 0.01). A value of 1.2 ng/ml AMH could be used to predict response to clomiphene citrate in obese women with PCOS (sensitivity 71%, specificity 65.7%). AMH production increases in women with PCOS compared to controls. AMH measurement could also be useful in the prediction of ovarian response to clomiphene citrate.     

The effect of weight loss program on serum anti-Müllerian hormone level in obese and overweight infertile women with polycystic ovary syndrome

We evaluated the predictive value of serum anti-Müllerian hormone (AMH) levels for improved menstrual cycles in response to dietary management in women with polycystic ovary syndrome (PCOS). In addition, we assessed the effect of a restricted calorie diet for 12 weeks on serum AMH levels. This intervention study was carried out at Rohan Institute, Tehran, Iran from 2013 to 2015. A total of 105 overweight and obese women with PCOS and reproductive impairment participated in a 12-week weight loss program (WLP). The serum AMH levels, weight, and menstrual cyclicity were assessed at baseline and post-intervention for all of the participants. A total of 90 patients completed the 12-week WLP. Of the 90 patients, 65 (72.2%) responded to the intervention with improvements in menstrual cyclicity. There were no significant differences in terms of age, baseline AMH levels, and other hormone profiles between responders and nonresponders. Responders had a significantly lower baseline body mass index (BMI) and waist circumference compared with nonresponders. These factors were the clinical predictors for a menstrual response after the intervention. The AMH levels did not significantly change after 12-week WLP despite the overall reduced weight; however, women who responded with improved reproductive function had a greater reduction in AMH levels.     

Response to ovulation induction treatments in women with polycystic ovary syndrome as a function of serum anti-Müllerian hormone levels

Journal of Assisted Reproduction and Genetics - To assess whether anti-Müllerian hormone (AMH) can predict response to ovulation induction (OI) with clomiphene citrate (CC), letrozole (LET),...     

Pregnancy and neonatal complications in women with polycystic ovary syndrome in relation to second-trimester anti-Müllerian hormone levels

Research questionAn association has been found between high anti-Müllerian hormone (AMH) levels during pregnancy and the development of polycystic ovary syndrome (PCOS)-like phenotypic traits in mouse offspring. The aim of this study was to determine whether AMH levels are associated with maternal testosterone levels, and whether high AMH concentration influences the risk of developing PCOS-related adverse pregnancy outcomes.DesignMaternal serum AMH, testosterone and sex hormone binding globulin levels were measured in blood samples taken in early second-trimester pregnancies from women with PCOS (n = 159) and healthy controls matched for body mass index (n = 320). Possible associations with preeclampsia, gestational hypertension, gestational diabetes, preterm birth and birthweight was explored by logistic and linear regression models.ResultsWomen with PCOS had higher AMH, higher total testosterone levels and higher free androgen index than controls (P < 0.001 for all three parameters). Among women with PCOS, high testosterone levels (B = 2.7; β = 0.26; P = 0.001) and low first trimester body mass index (B = –0.5; β = –0.17; P = 0.043) remained independently associated with AMH. High AMH levels were associated with decreased risk of gestational hypertension (adjusted OR 0.55; 95% CI 0.34 to 0.87), but no association was found with other adverse pregnancy outcomes or birthweight.ConclusionsWomen with PCOS had higher AMH levels during pregnancy compared with controls, but high AMH was not associated with increased risk of adverse pregnancy outcomes or birthweight.     

Anti-Müllerian hormone levels during hormonal contraception in women with polycystic ovary syndrome

OBJECTIVE: The use of oral contraceptive (OC) pills alters the characteristic features of polycystic ovary syndrome (PCOS) complicating the diagnosis of this disease. Anti-Müllerian hormone (AMH) levels are high in PCOS patients and are stable throughout the menstrual cycle in healthy subjects. This study examined the influence of hormonal suppression with OC therapy on the serum AMH levels in women with PCOS and with normal menstrual cycles. STUDY DESIGN: Thirty women with PCOS and 15 women with normal menstrual cycles were enrolled in this prospective study. Serum was collected from the subjects during the early follicular phase of the menstrual cycle and after the sixth cycle of oral contraceptive therapy, and stored frozen until assayed. The effect of OC therapy on the serum AMH, estradiol (E(2)), luteinizing hormone (LH), follicle-stimulating hormone (FSH), free testosterone, total testosterone, and dehydroepiandrosterone sulfate (DHEA-S) levels was studied. In addition, ovarian volume and follicle count were assessed. RESULTS: The serum AMH levels in PCOS patients were significantly higher than in healthy women at baseline (+/-S.D.; 5.49+/-2.26 and 1.93+/-0.51 ng/ml, respectively; p=0.001). After six cycles of OC therapy, no significant changes in the AMH levels were observed in either the PCOS patients or normally cycling women. Ultrasound showed significant reductions in ovarian volume and follicle number and size at 6 months in both groups. CONCLUSION: Although significant reductions were observed in ovarian volume and follicle number, 6 months of contraceptive therapy did not change the serum AMH concentration in either group. AMH may be considered a new marker in PCOS patients who are already on contraceptive treatment.     

Anti-Müllerian hormone and fertility disturbances in obese women and women with polycystic ovary syndrome

Anti-Müllerian hormone (AMH) belongs to a family of growth and differentiation factors beta (TGF-beta). In male fetuses AMH induces regression of Müller's ducts whereas in female ones this hormone plays an important role during adolescence and reproductive period. AMH participates in regulation of folliculogenesis by inhibiting the recruitment of prenatal and antral follicles. The aim of the present study was to summarize the current knowledge of the role of AMH in menstrual and fertility disturbances in obese women and those with polycystic ovary syndrome.     

The role of serum anti-Müllerian hormone (AMH) in the hormonal diagnosis of polycystic ovary syndrome

Abstract

Background: The study was performed to validate the threshold for anti-Müllerian hormone (AMH) that suggests the presence of polycystic ovaries in women with polycystic ovary syndrome (PCOS).

Methods: This prospective observational study included 59 infertile women: (A) 22 PCOS with hyperandrogenism (HA) and oligo-anovulation, (B) 15 suspected PCOS with either HA or oligo-anovulation and (C) 22 asymptomatic control women. The diagnosis of PCOS was made according to the NIH classification.

Results: For serum AMH and follicle number, respectively, the areas under the receiver operating characteristic curve (A versus C) were 0.97 and 0.93. The best compromise between specificity (95% and 91%) and sensitivity (95% and 82%) was obtained with threshold values of 33?pmol/l and 13 follicles, respectively. Using a serum AMH?>?33?pmol/l as a surrogate for either HA or oligo-anovulation in group B would lead to the diagnosis of PCOS in seven (46.6%) patients from this group.

Conclusions: Our data confirms that the AMH assay has a high diagnostic potential, providing that an appropriate threshold is used. AMH measurement may be included as an ultimate diagnostic criterion for the diagnosis of PCOS when either HA or anovulation is missing and/or when no reliable antral follicle count can be obtained.     

Expression of anti-Müllerian hormone in letrozole rat model of polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age with anti-müllerian hormone (AMH) two to three times higher, but the mechanism of increased AMH, excessive follicles and follicle stagnation in PCOS still needs further research.

Methods: Female Sprague–Dawley rats were treated with a gavage of 1.0?mg/kg of letrozole carboxymethylcellulose solution once daily for 21 consecutive days. Serum steroid concentrations, ovarian morphology, ovarian expression of AMH and AMH-RII protein were determined and their relationships were studied.

Results: According to the morphology and endocrinology, the letrozole model group was a successful PCOS model. Serum AMH and ovarian local expression of AMH and AMH-RII were both increased in letrozole model group. The elevated AMH had a positive correlation with T, growing follicle count and a negative correlation with body weight.

Conclusions: The letrozole model group is a good animal model for the study of AMH in PCOS patients with obesity or insulin resistance. The increased serum AMH level in PCOS is the consequence of the androgen-induced excess of small antral follicles. These results lead to the hypothesis that reducing AMH may become a therapeutic target of PCOS, which is worth further research.     

Accuracy of anti-Müllerian hormone and total follicles count to diagnose polycystic ovary syndrome in reproductive women

Objective

Recently, there was a new recommendation of ultrasonographic criteria to diagnosis polycystic ovary syndrome (PCOS). In addition, serum anti-Müllerian hormone (AMH) was proposed as a surrogate marker for diagnosis of PCOS, but AMH cut-off level for diagnosis of PCOS is unclear. This study aimed to investigate the accuracy of serum AMH and evaluate new ultrasonographic criteria, follicle number per ovary (FNPO) threshold ≥ 25 follicles and ovarian volume (OV) > 10 mL, for diagnosis of PCOS.

The role of anti-Müllerian hormone in predicting clomiphene citrate resistance in women with polycystic ovarian syndrome

Clomiphene citrate (CC) is the agent of first choice in polycystic ovarian syndrome; however, anovulation problem does not resolve in a quarter of them. Thus, we investigated the value of anti-Müllerian hormone (AMH) in the prediction of ovarian response to CC in women with the polycystic ovarian syndrome (PCOS). This prospective cohort study included 90 anovulatory women with PCOS who were given 50?mg/d CC. The patients who ovulated occupied the group of responders and the patients who did not ovulate in three cycles included in the CC-resistant group. AMH levels of both groups were compared. p?<?.05 was considered statistically significant. Patients who ovulated had significantly lower serum AMH concentrations compared with the resistant group (p?=?.001). After analyzing the ROC curve, serum AMH concentration was found to be a useful predictor of CC resistance with the sensitivity of 66% and the specificity of 89%, when the threshold AMH concentration was >12.38?ng/ml in PCOS patients. In the present study, we revealed that the higher the AMH level the poorer the CC response would be in PCOS patients, therefore we recommend measuring the AMH levels of all PCOS patients before planning any ovulation induction treatment to achieve the desired success.     

Is the suppressive effect of cyproterone acetate on serum anti-Müllerian-hormone levels in women with polycystic ovary syndrome stronger than under oral contraceptive pill?

Objective: To compare the suppressive effect of anti-androgen therapy by cyproterone acetate (CPA) and by oral contraceptive pill (OCP) on anti-müllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) in order to detect a putative direct anti-androgen effect on AMH excess.

Methods: This is a prospective longitudinal study including 58 women with PCOS between January 2010 and April 2014 at the Lille University Hospital. A total of 47 women with clinical hyperandrogenism were treated by CPA (50?mg/d was administered 20 days out of 28) and 11 women with PCOS but without clinical hyperandrogenism received OCP.

Result(s): Serum AHM levels at baseline were similar in CPA and OCP groups (median [5–95th percentiles]: 60.4?pmol/l [25.1–200.2] versus 58?pmol/l [27.6–100], respectively, p?=?0.39). After 3 months of treatment, serum AMH levels decreased significantly by 28%?±?20% and by 22%?±?27% in CPA and OCP groups, respectively. The decrease under both treatments was similar (p?=?0.48).

Conclusion(s): That any anti-androgen effect could be observed on AMH in our CPA group in addition to the gonadotropin-suppressing effect suggests that either androgens are not involved in AMH regulation or that they act by interfering with gonadotropin effects on granulosa cells.     

Anti-Müllerian hormone levels in women with polycystic ovarian syndrome compared with normal women of reproductive age in China

Objectives: Aim was to evaluate anti-Müllerian-hormone (AMH) in women with polycystic ovary syndrome (PCOS) comparing with normo-ovulatory women, and to assess for the first time AMH levels across reproductive lifespan in Chinese women.

Methods: Within the prospective cross-sectional study in PCOS cases and in normal subjects, AMH and other hormone levels were measured in early follicular phase in five age groups. Additionally ovarian ultrasound parameters were assessed.

Results: A total of 437 PCOS patients and 150 normo-ovulatory women matched by age were included. AMH levels were 2- to 3-fold higher in PCOS cases. In both groups AMH decreased with age in a non-linear pattern. In normo-ovulatory women AMH levels were relatively constant from 18 to 25 years and then declined with age. In contrast, AMH in PCOS cases declined with an increasing rate from 18 to 45 years, narrowing the difference in older women.

Conclusions: AMH may be a useful parameter to assess the severity and prognosis of PCOS since certain differences exist to normo-ovulatory women. Further studies may improve the understanding of the relationship between AMH levels and age, providing more scientific basis for fertility counselling for both healthy women and PCOS cases.