Adding metformin to lifestyle change lowers body mass index (BMI) and improves menstrual cyclicity, compared with lifestyle change alone, in women with polycystic ovary syndrome (PCOS), finds a recent meta-analysis.
It also indicates that metformin given alone for 6 months resulted in similar benefits in BMI to those achieved with lifestyle measures alone.
This is the first systematic review of randomized controlled trials exploring the role of metformin together with lifestyle change in PCOS and suggests the combination has a role to play in weight management of these patients.
The work is published online June 9 in Human Reproduction Update by Dr Negar Naderpoor (Monash University, Melbourne, Australia) and colleagues.
"These findings provide strong evidence advocating the beneficial effects of metformin in addition to lifestyle intervention on metabolic and reproductive features of PCOS," second author Dr Soulmaz Shorakae (Monash University) toldMedscape Medical News.
In particular, combining metformin with lifestyle modification might be beneficial "where compliance and sustainability with lifestyle modification are limited," she and her colleagues observe.
However, they acknowledge that their meta-analysis includes studies with "only small groups of subjects," and they stress that "future studies of appropriate size and duration are vital to clarify the role of metformin in PCOS management."
Asked to comment, Dr Stephen Franks (Imperial College London, United Kingdom) told Medscape Medical News that although the results "are encouraging, and there is logic to combining lifestyle with medication, there is as yet insufficient evidence to justify a widespread change of practice."
According to national and international guidelines, metformin is not a recommended first-line treatment in the management of PCOS, but its use is recommended by many specialist societies for certain symptoms of the syndrome or in cases where other treatment has failed.
For example, the US Endocrine Society recommends treatment with hormonal contraceptives as first-line therapy for menstrual abnormalities and hirsutism/acne associated with PCOS, but metformin is advised in women who cannot take hormonal contraceptives.
Adding Metformin Lowers BMI, Improves Menstrual Irregularity
Explaining the link between obesity and PCOS, Dr Shorakae said that excessive weight can exacerbate both metabolic and reproductive features of PCOS, leading to insulin resistance, impaired glucose tolerance, dyslipidemia, high androgen levels, ovulation dysfunction, and subfertility.
Insulin resistance is present in 65% to 80% of women with PCOS and is considered a key feature of the syndrome. "Metformin improves the insulin resistance in PCOS. Moreover, women with PCOS are at increased risk of type 2 diabetes where metformin would be the first-line therapy in addition to lifestyle modification."
The new review aimed to try to clarify the role of metformin in treating PCOS.
Lifestyle modification has been the mainstay of PCOS management, with beneficial effects on metabolic and reproductive features of the syndrome, Dr Shorakae noted, but implementation of lifestyle change is often hindered by low adherence and poor sustainability.
Previous research has suggested that metformin may augment the beneficial effects of lifestyle modification on weight management in these patients, and it has been shown to improve menstrual cyclicity and ovulation rate, but studies have been small and of short duration, she explained.
In their new review, the authors included 12 randomized controlled trials exploring the use of metformin, with or without lifestyle changes, and lifestyle interventions alone among 608 women with PCOS.
End points assessed were anthropometric, metabolic, reproductive, and psychological outcomes, including BMI. They compared lifestyle modification plus metformin with lifestyle modification plus placebo. They also compared metformin alone with lifestyle modification plus placebo.
"We found that adding metformin (1.5 to 2 g daily) to lifestyle modification resulted in a 0.73-kg/m2 lower BMI after 6 months [P = .0005] compared with lifestyle modification alone," report Dr Naderpoor and colleagues.
In addition, the combination of metformin and lifestyle modification was associated with lower subcutaneous adipose tissue (mean difference, -92.49 cm2 ; P = .01) and an increased number of menstrual cycles (mean difference, 1.06; P = .006) after 6 months of therapy compared with lifestyle modification alone, with persistent effects on menstruation at 12 months.
When metformin alone was compared with lifestyle, with or without placebo, BMI measurements were similar after 6 months, but testosterone level was lower with metformin.
"Our interpretation of this is that metformin alone is as effective as lifestyle intervention and that the combination of metformin with lifestyle intervention has additional benefits in management of PCOS," Dr Naderpoor and colleagues conclude.
Drilling Down to Identify Those Who Will Benefit Most From Metformin
However, the researchers stress that the subgroups that may benefit most from adding metformin to lifestyle change "and the benefits from longer-term addition of metformin to lifestyle modification beyond 6 months remain to be defined by future studies."
Currently, "in most cases women start metformin in preparation for conception, to lose weight, and to regulate menstruation and ovulation, and there is good evidence for adding metformin to other conventional ovulation-inducing therapies, especially where the conventional therapies fail to restore ovulation in women with PCOS," Dr Shorakae explained.
But "the therapeutic regimens are not well standardized, and there is no consensus on the length of therapy with metformin," she concluded.
Dr Shorakae, Dr Naderpoor, and coauthors have declared no relevant financial relationships, as has Dr Franks.Hum Reprod Update. Published online June 9, 2015. http://www.medscape.com/viewarticle/846877#vp_2