- There is no evidence to support the routine use of either metformin or a thiazolidenedione as first-line therapy for treatment of polycystic ovarian syndrome. (C)
- Diet and exercise are a better approach to PCOS treatment. A weight reduction of as little as 5% can help regulate the menstrual cycle and improve fertility, decrease insulin resistance, and reduce associated symptoms and comorbidities. (B)
Strength of recommendation (SOR)
- Good-quality patient-oriented evidence
- Inconsistent or limited-quality patient-oriented evidence
- Consensus, usual practice, opinion, disease-oriented evidence, case series
A 35-year-old woman with no past medical or surgical history presents to your office with complaints consistent with oligomenorrhea. She also reports a 15-pound weight gain over this past year.
Your patient is married and sexually active, but has never been pregnant. Her menarche was at age 12, and she says she has had irregular, infrequent menses over the past year, with 4 to 5 days of medium flow. Her social/family history is unremarkable.
She denies using any drugs, medications, supplements, or herbs. She had a recent TSH, fasting blood glucose, CBC, basic metabolic panel, and Pap smear done by her previous physician during a routine physical and all were normal.
On exam, your patient is clinically obese (abdominal adiposity) and notably hirsute. Her skin exam is also positive for hyperpigmented lichenified plaques around her neck and axilla, consistent with acanthosis nigricans. The rest of her exam is unremarkable.
Her signs and symptoms prompt you to suspect polycystic ovarian syndrome (PCOS), which you confirm after ruling out type 2 diabetes mellitus, thyroid disease, hyperprolactinemia, congenital adrenal hyperplasia, and androgen secreting tumors.
Your next step, of course, is treatment and you consider your options. Would pharmacological treatment with metformin or a thiazolidenedione (TZD) be appropriate?
An answer that may surprise you
There is no evidence to support the routine use of either metformin or a TZD as first-line therapy for the treatment of PCOS, based on a meta-analysis of randomized controlled clinical trials (strength of recommendation [SOR]: C). Instead, you should individualize your approach to achieve the patient’s short- and long-term goals, as well as to minimize complications and comorbidities. A good approach at this time would be to educate your patient on lifestyle changes, such as diet and exercise, since the evidence supports their use (SOR: B).1-4 A weight reduction of as little as 5% can help regulate the menstrual cycle and improve fertility, decrease insulin resistance, and reduce associated symptoms and comorbidities.4
PCOS is associated with features of insulin resistance, hyperandrogenism, and oligomenorrhea leading to anovulatory bleeding and infertility. Many—though not all—PCOS patients have ovarian cysts.
Why the shift away from metformin or a TZD?
This recommendation is based on a meta-analysis that we, the authors, recently conducted. The following review provides a more detailed look at our analysis of the evidence to date. But before we get to the study, let’s look at the syndrome that sparked our research.
Background Polycystic ovarian syndrome (PCOS) leads to a multitude of clinical and biochemical alterations in patients. Metformin and the thiazolidenediones (TZDs)—which have insulin sensitizing properties—are believed to be effective in minimizing the changes caused by this syndrome.
Objectives Our goal was to assess the evidence for the use of TZDs or metformin in the treatment of PCOS patients. In addition, we sought to assess and compare the effectiveness of metformin vs TZDs in the clinical and biochemical regression of PCOS based on available randomized controlled trials (RCTs).
Search strategy We searched Medline (January 1966 to January 2007), PubMed (January 1954 to January 2007), Google Scholar search engine (through January 2007), and reference lists of articles. We also contacted researchers and clinicians in the field.
Selection criteria We reviewed RCTs involving women diagnosed with PCOS (based on 1990 the National Institutes of Health Criteria) who were treated with either metformin or TZDs. Trials were limited to those that were testing only the effects of either of these agents as their primary endpoint.
Main results A total of 115 trials were obtained, of which only 33 trials met the inclusion criteria. Ultimately, 31 trials involving total 1892 patients were included in the analysis (23 metformin, 2 rosiglitazone, 1 pioglitazone, 5 troglitazone) with 2 unobtainable trials.
There was insufficient data to compare metformin to the TZDs in any parameter because the literature often contained inadequate quantitative data, or there were too few published trials. As a result, we performed the meta-analysis for metformin only.
Among the outcomes examined, the only statistically significant changes were minimal decreases with metformin in ovulation rates and luteinizing hormone to follicle stimulating hormone ratio (LH/FSH), and an increase in fasting insulin.
There was no clinically significant change with metformin in ovulation rate, pregnancy rate, body mass index, waist-to-hip ratio, hirsutism (F-G score), LH/FSH, fasting insulin, fasting blood glucose, total testosterone, free testosterone, androstenedione, and dehydroepiandrosterone sulfate.
Authors’ conclusions There is a paucity of data from RCTs to compare the effectiveness of metformin vs TZDs as well as the effects of either agent in treating the clinical and biochemical features of PCOS. Further research involving RCTs with larger sample sizes is needed before any recommendation can be made on the usefulness of these agents in the treatment of PCOS.