Metformin &amp; glitazones: Do they really help PCOS patients?

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Applied Evidence

Metformin & glitazones: Do they really help PCOS patients?

J Fam Pract. 2007 June;56(6):444-452

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References

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This systematic review provides a strong message that many of the trials were not of adequate methodological quality to make a definitive statement for clinical practice. In addition, most trials had a low sample size and used additional treatments with gonadotropins or ovulation induction agents that can yield altered results.

The primary aim of this study was to ascertain the evidence for the use of either TZDs or metformin in the treatment of patients with PCOS. This systematic review with the meta-analysis has found insufficient evidence to support the routine use of either. The secondary aim of this study was to obtain evidence to assess if either agent was superior in clinically reducing the various biochemical and clinical alterations due to this condition. Based on our analysis, we cannot claim either agent as superior.

Limitations

Few trials, sparse data

Any systematic review and meta-analysis will have inherent limitations as data from multiple trials, that might not be directly comparable, are combined to give an overview. Another limitation is that trials published in other languages were not included. We cannot exclude the possibility of selection or information bias because only one person reviewed all the articles to decide which would be included. However, we set the inclusion/exclusion criteria as well as endpoints very carefully prior to the study and literature search and had independent reviews by other authors during statistical analyses to minimize this problem.

The quality assessment of each trial is also subjective, even though strict inclusion/exclusion criteria were utilized. Assessing the efficacy of the TZDs could not be done as there were very few trials. Moreover, most of the TZD trials did not study or report on all the parameters. It is difficult to assess for publication bias or outliers and to justify combining the results when only a small number of trials are available or the data are sparse. In addition, although 5 trials with good sample size were available for troglitazone, this agent is no longer on the market, thus limiting clinical utility.

FAST TRACK

You should educate patients on diet and exercise, since multiple trials have justified their use

As most trials were not truly blinded upon careful review of the article, this may provide some bias. Furthermore, we could not conduct the meta-analysis for the gold standard method based on difference measures (before, after, and between treatment) due to data unavailability. Our alternative choice of analysis is justified based on the assumption that randomization will allow for baseline values in both groups to be approximately similar.

Finally, we used the SD or SE (or SEM) information as the original authors reported. Although SE is a function of sample size, SD is the population parameter so its variability should not be high. However, we found that the SDs varied considerably. It may be that the authors inadvertently used SD and SE interchangeably, thus leading to the heterogeneity of effect size.

Conclusions

Further study is needed

Carefully designed and sufficiently powered PCOS studies with large sample sizes, followed by the proper reporting of the study findings, are warranted. These studies, evaluating drug effects, should be done in a randomized placebo controlled fashion. Such trials should not be interfered with by using hormonal or ovulation induction agents other than the medication being studied. Diet and exercise should not be a part of the study’s design as these have been independently validated in similar contexts.⁴

For now, focus on lifestyle, and symptom-based treatment

PCOS encompasses a myriad of clinical and biochemical features, where each component adds to morbidity. The data, as per our study, are not sufficient to support the use of either of the studied agents in altering either the clinical or biochemical changes associated with the condition.

FAST TRACK

Carefully designed and sufficiently powered PCOS studies with large sample sizes are needed

Thus, clinicians should tailor their treatment regimen to the individual patient’s short- and long-term goals. Clinicians should also educate patients regarding lifestyle changes, such as diet and exercise, since multiple trials^1-4 have justified their use. Other options include symptom-based treatment, such as oral contraceptives for the regulation of menses or hirsutism.⁴

Acknowledgments

We wish to thank Dr Jan Groft, Dr Zakia Niruddin, Dr Marc Silverstein, and Dr Madhu Mazumdar for their efforts and guidance.

Funding/Support

This research was conducted without any outside funding or support.

Correspondence
Anush S. Pillai, DO, 424 Hahlo, Houston, TX, 77020; aspillai@tmh.tmc.edu.