Dataset Information

The effects of metformin on anti-Mullerian hormone levels in patients with polycystic ovary syndrome: a systematic review and meta-analysis

ABSTRACT:

Objective

To analyze whether metformin treatment in patients with polycystic ovary syndrome (PCOS) results in a decrease of anti-Müllerian hormone (AMH) levels, we reviewed and analyzed PCOS studies which evaluated serum AMH levels before and after metformin treatment.

Methods

This is a systematic review and meta-analysis of self-controlled clinical trials. Databases including PubMed, Embase, and Web of Science library were searched to identify eligible studies published before February 2023. Random-effects models were applied to assess standardized mean differences (SMDs) with 95% confidence intervals (95% CI).

Results

The electronic-based search retrieved 167 articles of which 14 studies (12 publications) involving 257 women with PCOS were included. In general, AMH levels decreased significantly after metformin treatment [SMD (95% CI) of -0.70 (-1.13 to -0.28); P = 0.001]. Metformin exhibited a strong inhibitory effect on AMH levels for PCOS patients with age less than 28 [SMD − 1.24, 95% CI − 2.15 to − 0.32, P = 0.008]. Additionally, AMH levels significantly slid down in PCOS patients with no more than 6 months metformin treatment [SMD − 1.38, 95% CI − 2.18 to − 0.58, P = 0.0007], or with no more than a dose of 2000 mg/day [SMD -0.70, 95% CI -1.11 to -0.28; P = 0.001]. Notably, suppressive effects of metformin treatment were merely observed in patients with AMH levels at baseline higher than 4.7 ng/ml [SMD − 0.66, 95% CI − 1.02 to − 0.31, P = 0.0003].

Conclusion

This meta-analysis provided quantitative evidence demonstrating that metformin significantly decreased AMH levels, especially for young patients and those with AMH levels at baseline higher than 4.7 ng/ml.

Trial registration

PROSPERO CRD42020149182.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13048-023-01195-1.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC10303859 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe majority of available studies on the AMH thresholds were not age-specific and performed the receiver operating characteristic curve (ROC) analysis, based on variations in sensitivity and specificity rather than positive and negative predictive values (PPV and NPV, respectively), which are more clinically applicable. Moreover, all of these studies used a pre-specified age categorization to report the age-specific cut-off values of AMH.MethodsA total of 803 women, including 303 PCOS patients and 500 eumenorrheic non-hirsute control women, were enrolled in the present study. The PCOS group included PCOS women, aged 20-40 years, who were referred to the Reproductive Endocrinology Research Center, Tehran, Iran. The Rotterdam consensus criteria were used for diagnosis of PCOS. The control group was selected among women, aged 20-40 years, who participated in Tehran Lipid and Glucose cohort Study (TLGS). Generalized additive models (GAMs) were used to identify the optimal cut-off points for various age categories. The cut-off levels of AMH in different age categories were estimated, using the Bayesian method.Main results and the role of chanceTwo optimal cut-off levels of AMH (ng/ml) were identified at the age of 27 and 35 years, based on GAMs. The cut-off levels for the prediction of PCOS in the age categories of 20-27, 27-35, and 35-40 years were 5.7 (95 % CI: 5.48-6.19), 4.55 (95 % CI: 4.52-4.64), and 3.72 (95 % CI: 3.55-3.80), respectively. Based on the Bayesian method, the PPV and NPV of these cut-off levels were as follows: PPV = 0.98 (95 % CI: 0.96-0.99) and NPV = 0.40 (95 % CI: 0.30-0.51) for the age group of 20-27 years; PPV = 0.96 (95 % CI: 0.91-0.99) and NPV = 0.82 (95 % CI: 0.78-0.86) for the age group of 27-35 years; and PPV = 0.86 (95 % CI: 0.80-0.94) and NPV = 0.96 (95 % CI: 0.93-0.98) for the age group of 35-40 years.ConclusionsApplication of age-specific cut-off levels of AMH, according to the GAMs and Bayesian method, could elegantly assess the value of AMH in discriminating PCOS patients in all age categories.