New PCOS guidelines: metformin underpins medical therapy

New international guidelines for the assessment and management of PCOS have included more than a dozen evidence-based recommendations and clinical practice points related to the use of metformin.

The guidelines, led by Australian researchers and approved by the NHMRC, recommend metformin in addition to lifestyle for the treatment of weight, hormonal and metabolic outcomes in adult women with PCOS.

They also recommend the addition of metformin to the combined oral contraceptive (COC) pill for women and overweight or obese adolescents where the pill and lifestyle do not achieve the desired goals.

Lead author Professor Helena Teede, from the Centre for Research Excellence in Polycystic Ovary Syndrome at Monash University, previously told the limbic during the consultation stage of the guidelines that metformin now plays much more of a role in guidelines.

The evidence shows that metabolic benefits are generally stronger in women with increased BMI – “an outcome of importance and value” to the women with PCOS who were involved in the guidelines development.

“In PCOS, evidence indicated that metformin is effective overall and /or in specified subgroups, in improving weight, BMI, WHR ratio, testosterone and TG in women with PCOS including those defined by Rotterdam criteria,” the guidelines state.

They also note that metformin may offer greater benefit in women with diabetes risk factors, impaired glucose tolerance or in high-risk ethnic groups.

Metformin use, in addition to lifestyle can also be considered in adolescents with symptoms or a clear diagnosis of PCOS.

“Gastrointestinal side effects were noted, but appear to be mild, self-limiting and could be minimised with lower metformin starting dose, extended release preparations or administration with food.”

“Concerns on vitamin B12 deficiency with longer term metformin use have also emerged, however more research is needed.”

The guidelines recommend the aromatase inhibitor letrozole as a first-line pharmacological therapy for improving fertility outcomes; with clomiphene and metformin having a role alone and in combination.

Usual doses of metformin range from 1500mg to 1700mg per day for non-fertility studies.

In a clinical practice point they note that while the use of such ovulation induction agents is off-label in many countries, “health professionals need to inform women and discuss the evidence, possible concerns and side effects”.

“Gonadotrophins with the addition of metformin, could be used rather than gonadotrophin alone, in women with PCOS with anovulatory infertility, clomiphene citrate-resistance and no other infertility factors, to improve ovulation, pregnancy and live birth rates,” the guidelines advise.

Adjunct metformin therapy – 1000 to 2550 mg daily – may also be used before and/or during follicle stimulating hormone ovarian stimulation in women with PCOS undergoing IVF therapy with a GnRH agonist protocol, to improve fertility outcomes.

“Women and health professionals would generally value an increased clinical pregnancy rate (with no evidence of a difference in miscarriage rate) and reduced ovarian hyperstimulation syndrome (with its associated morbidity and rarely mortality).”

Translation and education resources for women and health professionals are freely available with the guidelines.

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