The Efficacy of 24-Month Metformin for Improving Menses, Hormones, and Metabolic Profiles in Polycystic Ovary Syndrome

Po-Kai Yang; Chih-Yuan Hsu; Mei-Jou Chen; Mei-Yu Lai; Zheng-Rong Li; Chen-Hsin Chen; Shee-Uan Chen; Hong-Nerng Ho

doi:10.1210/jc.2017-01739

Therapeutics Metabolic and Endocrine Agents

The Efficacy of 24-Month Metformin for Improving Menses, Hormones, and Metabolic Profiles in Polycystic Ovary Syndrome

Yang PK, Hsu CY, Chen MJ, Lai MY, Li ZR, Chen CH, Chen SU, Ho HN

Published March 2018 The Journal of Clinical Endocrinology and Metabolism, 103(3), 890-899

DOI 10.1210/jc.2017-01739 PMID 29325133

RRM Academy Synopsis

Metformin was linked to more regular periods in women with PCOS

A study followed 119 women with polyendocrine metabolic ovarian syndrome (PMOS), formerly called PCOS, for 24 months. Metformin was linked to more regular periods. Most changes in weight and testosterone happened in the first 6 months.

Key Findings

Among 72 normal-weight women, the predicted share with regular menstrual cycles rose from 15% at baseline to 50% at 24 months (odds ratio 5.55, 95% CI 2.55 to 12.08).
Among 47 overweight women, the predicted share with regular cycles rose from 28% to 46% at 24 months (odds ratio 2.23, 95% CI 0.76 to 6.56).
Normal-weight women with elevated baseline testosterone showed the largest gain in regular cycles: odds ratio 7.21 (95% CI 2.35 to 22.17) at 6 months.
At 6 months, 42% to 47% of women in the four weight and testosterone subgroups had regular cycles. In the results tables, the overweight, normal-testosterone group kept improving after 6 months.
Body mass index, testosterone and luteinizing hormone were significantly lower by 6 months in both weight groups. Most measures showed no further significant change after 6 months.

Interpretation

This cohort study followed 119 women with polyendocrine metabolic ovarian syndrome (PMOS), formerly PCOS, tracking menstrual cycles by weight and baseline testosterone over 24 months on metformin. The authors chose this design and cite ethical concerns about long-term placebo use. The authors note that follow-up fell to 37% by 24 months; results among the women who remained were generally compatible with the full group. The authors call the reason for different responses between subgroups unknown. The findings support larger studies of metformin's effect on menstrual regularity in women with PMOS/PCOS.

RRM Context

PMOS / PCOS includes several types. These women responded differently by weight and testosterone. Restorative reproductive medicine looks for the cause behind each woman's hormone pattern. In this study, a cycle counted as regular only after a temperature chart or progesterone test showed ovulation.

Our editorial summary of this paper, not the article's abstract.

Abstract

Context

The long-term effects of metformin in women with polycystic ovarian syndrome (PCOS) are inadequately studied.

Objective

The effects of metformin on women with PCOS during 24 months with respect to menses, hormones, and metabolic profiles are assessed.

Design

Prospective cohort.

Setting

A reproductive endocrinology clinic in a university-affiliated medical center.

Patients

One hundred nineteen women with PCOS, defined by the Rotterdam criteria, were enrolled.

Intervention

Metformin was given daily for 24 months.

Main Outcome Measures

The primary outcome was the proportion of patients with regular menstruation during treatment. Changes in anthropometric, hormonal, and metabolic parameters were also assessed. Analyses were performed using segmented regression analysis with a generalized estimating equation methodology. Outcomes are expressed as magnitude of change from the baseline.

Results

Both overweight (OW) and normal-weight (NW) women with PCOS had increased menstrual frequency and decreased body mass index (BMI), testosterone, and luteinizing hormone levels in the first 6 months. Further stratification showed that NW women exhibiting elevated testosterone at baseline had the largest magnitude of improvement at 6 months [odds ratio (OR), 7.21; 95% confidence interval (CI), 2.35 to 22.17], whereas OW patients with normal testosterone were most likely to achieve normal menses at 12 months (OR, 0.63; 95% CI, 0.47 to 0.77).

Conclusions

Metformin was associated with improvements in the menstrual cycle and most hormonal profiles in OW and NW women with PCOS during 24 months of treatment. Most parameters reached maximal response and steady-state after 6 months. Phenotypic differences in baseline BMI and testosterone level can be used as patient selection criteria or treatment prognostics.

Topics

Therapeutics › Metabolic and Endocrine Agents › Insulin Sensitizing Agents · Reproductive Endocrinology › Ovarian Hormones › Androgens · Menstrual Cycle › Cycle Disorders › Ovulatory Disturbances

Po-Kai Yang, Chih-Yuan Hsu, Mei-Jou Chen, Mei-Yu Lai, Zheng-Rong Li, Chen-Hsin Chen, Shee-Uan Chen, Hong-Nerng Ho

P Yang, C Hsu, M Chen, M Lai, Z Li, C Chen, S Chen, H Ho

PMID 29325133 29325133 DOI 10.1210/jc.2017-01739 10.1210/jc.2017-01739 Yang et al. 2018, Yang 2018

Keywords

Adult, Anthropometry/methods, Body Mass Index, Drug Administration Schedule, Female, Humans, Hypoglycemic Agents/administration & Dosage/therapeutic Use, Longitudinal Studies, Luteinizing Hormone/blood, Menstruation/drug Effects, Metformin/administration & Dosage/therapeutic Use, Polycystic Ovary Syndrome/blood/drug Therapy/physiopathology, Prospective Studies, Testosterone/blood, Young Adult, Hypoglycemic Agents, Testosterone, Luteinizing Hormone, Metformin

The Efficacy of 24-Month Metformin for Improving Menses, Hormones, and Metabolic Profiles in Polycystic Ovary Syndrome

Metformin was linked to more regular periods in women with PCOS

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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Keywords