Well-known drug has less risk for preterm delivery in PCOS

Metformin significantly reduces the risk of late miscarriages and preterm births for women with PCOS. But the drug does not work to prevent gestational diabetes, according to a large Nordic study from NTNU and St. Olavs hospital.

Metformin can halve the risk of late miscarriage and preterm births for women with polycystic ovary syndrome (PCOS).

PCOS occurs in 10 to 15 per cent of all women. The symptoms are irregular menstrual periods, increased levels of male sex hormones and small ovarian blisters. In addition, many women with PCOS are overweight. Women with PCOS also have an increased incidence of reduced fertility, miscarriages, gestational diabetes, premature births and pre-eclampsia.

In addition to having a lower risk of miscarriages and premature births,  women who received metformin also gained less during pregnancy, researchers found. Photo: Colourbox

“In pregnant women with PCOS, treatment with metformin from the end of the first trimester may reduce the risk of late miscarriages and preterm births,” states Professor Eszter Vanky.

Professor Vanky leads the research group “Women’s Health – PCOS” at NTNU’s Department of Clinical and Molecular Medicine. A new article appearing in the journal Lancet Diabetes & Endocrinology presents the results of nearly two decades of research from NTNU and St. Olav’s hospital. Consultant Tone S. Løvvik is the first author, and the study is part of her doctoral work. Professor Sven M. Carlsen is co-supervisor.

However, the research group surprisingly found no reduction of gestational diabetes among this cohort of women with PCOS.

Examined 800 women

From 2000 to 2017, the research group carried out three controlled studies of nearly 800 pregnant women with PCOS. The studies were conducted at 15 hospitals in Norway, 4 hospitals in Sweden and one in Iceland. Half of the women were given metformin (2000 milligrams daily) from first trimester to delivery. The rest of the women were given a placebo.

In addition to a lower risk of late miscarriage and preterm births, the researchers also found that the women who received metformin gained less weight during pregnancy.

A higher level of male sex hormones is associated with several of the symptoms of PCOS. The causes of the condition are not known, but may be related to lifestyle, inheritance and intrauterine foetal life.

The group found no effect on pre-eclampsia, pregnancy-induced high blood pressure or to what extent newborns of women with PCOS needed intensive care.

PCOS occurs in 10 to 15 per cent of all women. Photo: Colourbox

No effect on diabetes

“Perhaps the most remarkable finding was that metformin had no effect whatsoever on either the incidence or severity of gestational diabetes,” Vanky notes.

Metformin is a well-known drug used in the treatment of type 2 diabetes, and in some countries regarded as equivalent to insulin as a first-line drug therapy for gestational diabetes.

The three studies that form the basis of the conclusion were carried out according to Good Clinical Practice principles and will have an impact on the follow-up and treatment of pregnant women with PCOS and likely also of other pregnant women.

Another part of the study followed up children of mothers with PCOS who used metformin, and a control group that was given a placebo.

The work was financed by the Research Council of Norway, St. Olavs Hospital, NTNU and Novo Nordisk.

Source: Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial Tone S Løvvik, PhD, Prof Sven M Carlsen, MD, Øyvind Salvesen, PhD, Berglind Steffensen, MD, Prof Marie Bixo, MD, Prof Francisco Gómez-Real, PhD et al. DOI: https://doi.org/10.1016/S2213-8587(19)30002-6