Comparing the individual effects of metformin and rosiglitazone and their combination in obese women with polycystic ovary syndrome: a randomized controlled trial

High-dosage metformin plus lifestyle modification should be recommended for obese, insulin-resistant women with polycystic ovary syndrome, and rosiglita- zone alone or combined with low-dose metformin for those with abnormal lipid profiles.

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Volume 113, Issue 1, Pages 197–204

Authors:

Yujing Li, M.Med., Jing Tan, M.D., Qiuyi Wang, M.D., Changling Duan, M.D., Yuanyuan Hu, M.D., Wei Huang, M.D., Ph.D.

Abstract:

Objective

To compare the effects of metformin, rosiglitazone, and their combination in obese polycystic ovary syndrome (PCOS) patients with insulin resistance.

Design

Prospective randomized controlled trail.

Setting

Tertiary teaching hospital.

Patient(s)

Obese Chinese women (body mass index [BMI] ≥25 kg/m2) with insulin resistance who fulfilled the Rotterdam criteria of PCOS.

Intervention(s)

In group 1, 68 patients administered metformin (1,500 mg/day); in group 2, 67 patients administered rosiglitazone (4 mg/day); in group 3, 69 patients administered metformin (1,000 mg/day) and rosiglitazone (4 mg/day) for 6 months, all with the same diet and regular exercise lifestyle recommendation.

Main Outcome Measure(s)

Average menstrual interval, anthropometric measurements, androgen-related parameters, and metabolic features of insulin, carbohydrates, and lipids, with intention-to-treat analysis.

Result(s)

The baseline parameters showed no statistically significant differences. After the 6-month treatment, most participants showed an improved menstrual pattern. There were statistically significant decreases in acne scores, weight, BMI, waist circumference, waist-to-hip ratio, and serum testosterone. The metabolic indexes of insulin, carbohydrates, and lipids were improved obviously compared with the baseline in each group. Among the three groups, the patients administered 1,500 mg/day metformin experienced greater reductions in weight. However, the rosiglitazone users (alone or combined with metformin) showed a more notable decline in total cholesterol and triglyceride levels.

Conclusion(s)

Considering the benefits of metformin on weight loss, high-dose metformin (1,500 mg/day) along with lifestyle modification should be recommended for obese, insulin-resistant women with PCOS. Rosiglitazone alone or combined with low-dosage metformin plus lifestyle modification should be considered for the women with abnormal lipid profiles.

Clinical Trial Registration Number

ChiCTR-TRC-13003642 (Chinese Clinical Trial Registry).


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

3 Comments

Go to the profile of M. Blake Evans
M. Blake Evans about 1 month ago

Thank you to the authors for a clinically useful study in an extremely common diagnosis that we see on a daily basis.  The findings make me think more about how we should be utilizing metformin in our daily practice. As we know, the ASRM Practice Committee documents summarize that there is good evidence that metformin + CC improves ovulation and clinical pregnancy rates, fair evidence that pretreatment with metformin for at least 3 months followed by ovulation induction increases live-birth rate, and good evidence that metformin decreases the OHSS risk in PCOS patients. In addition to recommending metformin for the obese and insulin resistant PCOS patients, as was done in the study at hand, I'm inclined to recommend metformin to ALL PCOS patients prior to undergoing infertility treatment. I'm interested to hear what others think as well as the authors.

Go to the profile of Luis Hoyos
Luis Hoyos about 1 month ago

I agree with you. Based on my understanding of the evidence, pretreatment with metformin among patients with PCOS seems appropriate before fertility treatment. Having said that, I have my doubts about using it indiscriminately among all PCOS patients given the phenotypic heterogeneity particularly if using Rotterdam criteria. For example, I would feel entirely comfortable doing it among the obese and those that fulfill NIH criteria since they are likely to have some degree of insulin resistance. However, I would be less inclined to do so in phenotype D (oligoanovulation + PCOM) since there could be some overlap with hypothalamic dysfunction which may end up in metformin overtreatment when you may not need it. An alternative would be to test for insulin resistance in patients whom you have diagnosed PCOS, the downside is that there is no real validated method to do this in clinical practice although some would argue to use the insulin levels during an 2 h OGTT and the PCOS chapter in Yen & Jaffe proposes some thresholds to make this diagnosis. What are your thoughts in terms of insulin resistance evaluation and metformin use among different PCOS phenotypes?

 

Go to the profile of M. Blake Evans
M. Blake Evans about 1 month ago

Thanks for the reply, Luis. In those with risk factors for impaired glucose tolerance (family Hx, overweight, hyperandrogenism phenotype, obviously acanthosis) I'll get the recommended 75 g OGTT, but otherwise not perform any insulin testing. My thought is that if I'm already obtaining at least a TSH in someone who has AUB-O and/or has hyperandrogenism as part of my PCOS work up, then that would at least eliminate one main aspect of hypothalamic dysfunction if I took a "meformin for all" approach. To answer your question on metformin in phenotypes, I typically think about prescribing in the obese (or of course IGT) or NIH phenotype, as you mentioned. If they aren't obese, had an AFC of 45 and ultimately went to IVF, my thought is that would it would be nice to already have metformin on board to reduce OHSS risk so I'm not backpedaling once we start stimulating. I appreciate the insight!