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ABSTRACT: Objective
The consequences of the recently proposed International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria for gestational diabetes mellitus (GDM) in women with polycystic ovary syndrome (PCOS) are not known. We compared prevalence rates and risk factors for GDM in PCOS women according to both the WHO and modified IADPSG criteria.DesignPost hoc analyses from a randomized multicenter study.Methods
Fasting and 2-hour plasma glucose was measured during a 75 g oral glucose tolerance test. GDM was diagnosed according to both the WHO andmodified IADPSG criteria.ResultsGDM prevalence according to the WHO and modified IADPSG criteria was 9.2 % and 15.0 % at week 12, 18.7 % and 18.7 % at week 19 and 25.6 % and 24.2 % at week 32. Shorter stature and increased insulin levels correlated to WHO-GDM, but not to modified IADPSG-GDM, at week 12 and 19. Less weight gain in pregnancy predicted GDM according to both criteria. GDM diagnosis correlated to less maternal weight loss the first year post-partum.Conclusions
No difference was found in GDM prevalence between the two criteria used. Less weight gain in pregnancy associated with GDM independent of which diagnostic criteria were used. Reduced weight loss the first post-partum year in women with GDM raises the question of whether the GDM diagnosis per se or the fact that these women loose less weight after pregnancy predicts later diabetes mellitus.
European Journal of Endocrinology 05/2013; · 3.42 Impact Factor
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ABSTRACT: BACKGROUND:The impact of metformin medication in pregnant women with polycystic ovary syndrome on weight gain during pregnancy and after delivery and the impact on growth of the offspring are essentially unexplored.METHODS:This is a follow-up study of a randomized controlled trial (The Metformin treatment in pregnant PCOS women study), conducted in 11 secondary care centers. Women with PCOS were randomized to metformin (2000 mg daily) or placebo from first trimester to delivery. Questionnaires were sent to 256 participants 1 year postpartum. Maternal weight development in pregnancy and the first year after delivery and offspring anthropometry at birth and weight 1 year postpartum were registered.RESULTS:Women randomized to metformin gained less weight during pregnancy compared with those in the placebo group. In the newborns, there was no difference between the 2 groups in weight or length. One year postpartum, women who used metformin in pregnancy lost less weight and their infants were heavier than those in the placebo group (10.2 ± 1.2 kg vs 9.7 ± 1.1 kg, P = .003).CONCLUSIONS:Women randomized to metformin were heavier in the first trimester, gained less weight in pregnancy, and lost less weight in the first year postpartum compared with women randomized to placebo. Children exposed to metformin weighed more at 1 year of age.
PEDIATRICS 10/2012; · 4.47 Impact Factor
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ABSTRACT: Objectives. To investigate the possible long-term effects of metformin exposure on growth and development of the offspring born to mothers with polycystic ovary syndrome (PCOS). The drug passes through the placenta and can potentially influence the fetus. Patients and methods. This is a follow-up study of a randomized, controlled trial on PCOS women, randomized to metformin or placebo in pregnancy. Out of 37 children aged 7-9 years, 25 agreed to participate. Primary outcome measures were growth, body composition and metabolic parameters. Results. There were no differences in height, weight or body composition between those exposed to metformin and those exposed to placebo. We found a higher fasting glucose level in the metformin group (4.93 mmol/L vs. 4.60 mmol/L, p = 0.04). In the metformin group there was a trend towards higher systolic blood pressure (106 mmHg vs. 101 mmHg, p = 0.05) and a lower LDL cholesterol level (2.42 mmol/L vs. 2.99 mmol/L, p = 0.07). Conclusion. Metformin exposure during fetal life does not seem to influence growth and body composition at the age of 8 years. A higher fasting glucose level and a possible higher systolic blood pressure and lower LDL cholesterol level in the metformin group may be coincidental and should be further explored.
Scandinavian journal of clinical and laboratory investigation 08/2012; 72(7):570-5. · 1.38 Impact Factor
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ABSTRACT: STUDY QUESTION: Can anti-Müllerian hormone (AMH) level replace the morphologic description in the diagnosis of polycystic ovary syndrome (PCOS) and what is the relationship between AMH and different diagnostic criteria of PCOS? SUMMARY ANSWER: AMH may be a good substitute for polycystic ovarian morphology (PCOM) in diagnosing PCOS. WHAT IS KNOWN ALREADY: AMH has been suggested as an alternative to antral follicle count (AFC) in diagnosing PCOS. Cut-off values for AMH studied so far show an acceptable specificity but a rather poor sensitivity, leaving up to one-third of PCOS women undiagnosed. STUDY DESIGN, SIZE, DURATION: We used data from a cross-sectional, case-control study on women with prior preterm birth and their controls, i.e. women with prior full-term birth. Among 262 women, 56 met the Rotterdam criteria (PCOS-R) and 44 the Androgen Excess-PCOS Society (PCOS-AES) criteria of PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fasting blood samples were collected, a transvaginal ultrasound investigation and a clinical examination were performed. PCOS-R and PCOS-AES were re-diagnosed by replacing PCOM with AMH. Main outcome measures were the prevalence of PCOS, PCOM, hirsutism, oligoamenorrhoea and serum levels of AMH and androgens. MAIN RESULTS AND THE ROLE OF CHANCE: When replacing PCOM with AMH, the specificity and sensitivity for identifying PCOS were 97.1 and 94.6% according to the PCOS-R criteria and 97.2 and 95.5% according to the PCOS-AES criteria, respectively, at an AMH cut-off value of 20 pmol/l. LIMITATIONS, REASONS FOR CAUTION: The results need to be confirmed when international standards and methods for AMH measurements are established. WIDER IMPLICATIONS OF THE FINDINGS: AMH may be a good substitute for PCOM in diagnosing PCOS. STUDY FUNDING/COMPETING INTEREST(S): This study was financed by the Cooperative of Central Norway Regional Health Authority and Norwegian University of Science and Technology. The authors have no interests to disclose. TRIAL REGISTRATION NUMBER: This study is registered at www.clinicaltrials.gov as NCT01355536.
Human Reproduction 06/2012; 27(8):2494-502. · 4.47 Impact Factor
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ABSTRACT: To explore the possible effect of metformin on maternal and fetal androgens and antimüllerian hormone (AMH) levels at birth and to study the predictors of maternal and fetal AMH levels.
Substudy of a randomized controlled trial (the PregMet study).
University hospital.
Women with polycystic ovary syndrome (PCOS) and their newborns (n = 132).
Metformin, 2,000 mg/daily, or placebo from the first trimester until delivery.
Androgens and AMH levels in maternal venous serum and in umbilical vein and artery serum.
Except for the increased free testosterone index (FTI) in the umbilical artery in boys, metformin did not influence maternal or fetal androgens, or AMH levels. The maternal body mass index (BMI) was a negative and FTI a strong positive predictor of maternal AMH levels. Maternal androgens and AMH levels did not correlate to fetal gender. In girls, gestational age, birth weight, or maternal androgens did not correlate to the AMH levels. In boys, birth weight was negatively correlated to the AMH levels.
Except for FTI, which was higher in boys, metformin had no impact on maternal or fetal androgen levels or the level of AMH. Fetal AMH, as a surrogate marker for ovarian development, was unaffected by maternal androgens. Birth weight and gestational age had no impact on AMH levels in girls; in boys, AMH probably reflects the physiologic variations due to birth weight.
NCT00159536 (www.clinicaltrials.gov).
Fertility and sterility 12/2011; 97(2):509-15. · 3.97 Impact Factor
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Eszter Vanky,
Solhild Stridsklev,
Kristin Skogøy,
Odrun Kleggetveit,
Sissel Hjelle,
Philip V Brandis,
Torunn Eikeland,
Karin Flo,
Kristin Flaten Berg,
Gabor Bunford,
Agnethe Lund,
Cecilie Bjerke,
Ingunn Almås,
Ann Hilde Berg,
Anna Danielsson,
Gulim Lahmami,
Sven M Carlsen
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ABSTRACT: To describe patient characteristics according to different diagnostic criteria in early pregnancy, in women with polycystic ovary syndrome (PCOS).
Descriptive, cross-sectional study of 257 women with PCOS in the first trimester of pregnancy.
Data from a multicenter trial at the time of inclusion.
257 PCOS women with singleton pregnancies.
Investigator-administrated questionnaires were filled out. Clinical examination was performed by the investigators. Fasting blood samples were collected.
Biometric data, androgens, glucose and insulin levels.
Women who met the National Institutes of Health (NIH) criteria for PCOS had higher body mass index (BMI), testosterone, dehydroepiandrostenedione, free testosterone index (FTI) and insulin levels compared with those who only met the Rotterdam consensus criteria. Adjusted for age and BMI, only testosterone and FTI were higher in those who met the NIH criteria. BMI was a strong, independent predictor of both systolic and diastolic blood pressure in early PCOS pregnancy, while both FTI and fasting insulin were independent predictors of systolic blood pressure. Twenty-two (9%) of the participants had gestational diabetes mellitus in the first trimester of pregnancy.
In the first trimester, PCOS women diagnosed according to NIH criteria were more metabolically and endocrinologically abnormal compared with those who only met the Rotterdam consensus criteria. BMI and FTI were independent predictive factors for blood pressure. There was a high prevalence of gestational diabetes mellitus in early PCOS pregnancies.
Acta Obstetricia Et Gynecologica Scandinavica 01/2011; 90(4):398-404. · 1.77 Impact Factor
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Eszter Vanky,
Solhild Stridsklev,
Runa Heimstad,
Pål Romundstad,
Kristin Skogøy,
Odrun Kleggetveit,
Sissel Hjelle,
Philip von Brandis,
Torunn Eikeland,
Karin Flo,
Kristin Flaten Berg,
Gabor Bunford,
Agnethe Lund,
Cecilie Bjerke,
Ingunn Almås,
Ann Hilde Berg,
Anna Danielson,
Gulim Lahmami,
Sven Magnus Carlsen
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ABSTRACT: Metformin is widely prescribed to pregnant women with polycystic ovary syndrome (PCOS) in an attempt to reduce pregnancy complications. Metformin is not approved for this indication, and evidence for this practice is lacking.
Our objective was to test the hypothesis that metformin, from first trimester to delivery, reduces pregnancy complications in women with PCOS.
We conducted a randomized, placebo-controlled, double-blind, multicenter study at 11 secondary care centers.
The participants were 257 women with PCOS, in the first trimester of pregnancy, aged 18-42 yr.
We randomly assigned 274 singleton pregnancies (in 257 women) to receive metformin or placebo, from first trimester to delivery.
The prevalence of preeclampsia, gestational diabetes mellitus, preterm delivery, and a composite of these three outcomes is reported.
Preeclampsia prevalence was 7.4% in the metformin group and 3.7% in the placebo group (3.7%; 95% CI, -1.7-9.2) (P=0.18). Preterm delivery prevalence was 3.7% in the metformin group and 8.2% in the placebo group (-4.4%; 95%, CI, -10.1-1.2) (P=0.12). Gestational diabetes mellitus prevalence was 17.6% in the metformin group and 16.9% in the placebo group (0.8%; 95% CI, -8.6-10.2) (P=0.87). The composite primary endpoint prevalence was 25.9 and 24.4%, respectively (1.5%; 95% CI, -8.9-11.3) (P=0.78). Women in the metformin group gained less weight during pregnancy compared with those in the placebo group. There was no difference in fetal birth weight between the groups.
Metformin treatment from first trimester to delivery did not reduce pregnancy complications in PCOS.
The Journal of clinical endocrinology and metabolism 10/2010; 95(12):E448-55. · 6.50 Impact Factor
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Acta Obstetricia Et Gynecologica Scandinavica 03/2010; · 1.77 Impact Factor
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ABSTRACT: Breastfeeding depends on endocrine changes during pregnancy. The association between gestational hormones and lactation has been sparsely investigated. Previously, androgens were used for lactation inhibition. We investigated a possible association between second trimester maternal androgen levels and breastfeeding.
Prospective observational study.
University hospital setting. POPULATION. Women from a random sample of pregnancies (n = 63) and from a group with an increased risk for giving birth to a small-for-gestational age newborn (n = 118) were included. All participants had singleton pregnancies and one or two previous births.
Maternal androgen levels were measured in gestational week 25. The association with reported breastfeeding was explored by univariate and multivariate linear regression analyses. Analyses were adjusted for factors known to be associated with breastfeeding.
Breastfeeding at six weeks, three months, and six months postpartum.
In the random group, breastfeeding at three and six months was negatively associated with maternal testosterone, androstendione, and free testosterone index levels. After correction for maternal age, education and smoking, breastfeeding at both three and six months was negatively associated with the free testosterone index. In the group of women with an increased risk for giving birth to a small-for-gestational age newborn, breastfeeding at six weeks and three months was associated negatively with maternal dehydroepiandrosterone and this association persisted after correction for maternal age, education, and smoking.
Maternal androgen levels in mid-pregnancy are negatively associated with breastfeeding.
Acta Obstetricia Et Gynecologica Scandinavica 11/2009; 89(1):87-94. · 1.77 Impact Factor
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ABSTRACT: To investigate pregnancy complications and offspring sex ratio according to mode of conception in women with polycystic ovary syndrome (PCOS).
Retrospective, descriptive study.
Tertiary, university hospital.
A total of 176 women with PCOS diagnosed according to the Rotterdam criteria.
Women with PCOS who have participated in one or more clinical studies were invited to answer a questionnaire on the mode of conception, pregnancy complications, gestational length and offspring gender. A total of 139 women responded. Data were quality checked against hospital files.
Fertility, mode of conception, offspring gender and pregnancy complications.
More than half (54%) of the singleton pregnancies were conceived spontaneously. More complications were seen in pregnancies achieved while using metformin than without (p = 0.02). Compared to spontaneous conception, more boys than girls were born in singleton pregnancies after in vitro fertilization/intracytoplasmatic sperm injection treatment (p = 0.004).
In women with PCOS the mode of conception may influence both the rate of pregnancy complications and the offspring sex ratio.
Acta Obstetricia Et Gynecologica Scandinavica 01/2009; 88(11):1261-6. · 1.77 Impact Factor
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ABSTRACT: We studied a possible association between pregnancy complications and blood/serum levels of haemoglobin, C-reactive protein, sex hormones and lipids in women with polycystic ovary syndrome.
Twenty-one women with polycystic ovary syndrome were followed prospectively from the first trimester to delivery. Women with pregnancy complications (n=10) were compared to women without complications (n=11). Outcome measures were blood/serum levels of haemoglobin, C-reactive protein, dehydroepiandrosterone sulphate, androstenedione, testosterone, sex hormone binding globulin, free testosterone index, oestrogens and lipids.
Haemoglobin levels were higher in complicated pregnancies compared to uncomplicated pregnancies throughout the complete pregnancy, while C-reactive protein levels were higher for complicated pregnancies at gestational weeks 19 and 32. Serum levels of lipids, androgens and oestrogens did not differ throughout pregnancy.
In women suffering from polycystic ovary syndrome, pregnancy complications were associated with elevated blood/serum levels of haemoglobin and C-reactive protein. Androgen, oestrogen and lipid levels did not differ between groups.
Scandinavian Journal of Clinical and Laboratory Investigation 02/2008; 68(5):421-6. · 1.38 Impact Factor
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ABSTRACT: To investigate the breastfeeding rate in new mothers with polycystic ovary syndrome (PCOS).
Case-control study. Thirty-six women with PCOS and 99 controls matched for age, gestational length and parity, answered a questionnaire. Breastfeeding at one-, three- and six-months postpartum was registered and the two groups were compared. In the women with PCOS, androgen levels through pregnancy were analysed and related to breastfeeding rate.
At one-month postpartum, 27 (75%) of the women with PCOS were breastfeeding exclusively, whereas five (14%) did not breastfeed at all. Among controls, 88 (89%) were breastfeeding exclusively and two (2%) did not breastfeed (p=0.001). At three- and six-months postpartum, breastfeeding was equal in the two groups. Problems with sore nipples and seeking professional lactation support were also equal. Dehydroepiandrosterone-sulphate levels at gestational week 32 and 36 showed a weak negative association with breastfeeding in PCOS women. Breastfeeding rate was not associated with maternal gestational levels of androstenedione, testosterone, sex-hormone binding globulin, or free testosterone index in PCOS.
Women with PCOS appear to have a reduced breastfeeding rate in the early postpartum period. Possibly, gestational dehydroepiandrosterone-sulphate might negatively influence breastfeeding rate in women with the syndrome.
Acta Obstetricia Et Gynecologica Scandinavica 02/2008; 87(5):531-5. · 1.77 Impact Factor
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ABSTRACT: Objective . We studied a possible association between pregnancy complications and blood/serum levels of haemoglobin, C-reactive protein, sex hormones and lipids in women with polycystic ovary syndrome. Material and methods . Twenty-one women with polycystic ovary syndrome were followed prospectively from the first trimester to delivery. Women with pregnancy complications (n = 10) were compared to women without complications (n = 11). Outcome measures were blood/serum levels of haemoglobin, C-reactive protein, dehydroepiandrosterone sulphate, androstenedione, testosterone, sex hormone binding globulin, free testosterone index, oestrogens and lipids. Results . Haemoglobin levels were higher in complicated pregnancies compared to uncomplicated pregnancies throughout the complete pregnancy, while C-reactive protein levels were higher for complicated pregnancies at gestational weeks 19 and 32. Serum levels of lipids, androgens and oestrogens did not differ throughout pregnancy. Conclusion . In women suffering from polycystic ovary syndrome, pregnancy complications were associated with elevated blood/serum levels of haemoglobin and C-reactive protein. Androgen, oestrogen and lipid levels did not differ between groups.
Scandinavian Journal of Clinical and Laboratory Investigation 01/2008; · 1.38 Impact Factor
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ABSTRACT: Women with polycystic ovary syndrome have elevated homocysteine levels. Elevated homocysteine levels associate with pregnancy complications. Women with polycystic ovary syndrome are often treated with metformin, a drug that may increase homocysteine levels. Hence, we investigated the effect of metformin treatment on homocysteine levels in nonpregnant and pregnant women with polycystic ovary syndrome.
Two prospective randomized placebo-controlled studies included women with polycystic ovary syndrome in a university hospital setting. Sixty-three infertile women were treated with metformin 1,000 mg bid or placebo for 16 weeks and 38 pregnant women with metformin 850 mg bid or placebo from the first trimester and throughout pregnancy. All the women had polycystic ovary syndrome and all participants received diet and lifestyle advice, and oral folate and vitamin B12 substitution, and a daily oral multivitamin tablet. The main outcome measures were serum levels of homocysteine, folate, and vitamin B12.
Serum homocysteine levels were unaffected by metformin treatment both in nonpregnant and pregnant women with polycystic ovary syndrome. However, in nonpregnant women both serum folate and vitamin B12 levels decreased with treatment. At inclusion in nonpregnant women, serum homocysteine levels associated negatively with serum levels of folate and methyl malonic acid and positively with free testosterone index. No such associations were seen in pregnant women.
Metformin treatment in women with polycystic ovary does not increase serum homocysteine levels in the nonpregnant or the pregnant state.
Acta Obstetricia Et Gynecologica Scandinavica 02/2007; 86(2):145-50. · 1.77 Impact Factor
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Fertility and sterility 12/2006; 86(5):1551-2; author reply 1552-3. · 3.97 Impact Factor
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ABSTRACT: In women with polycystic ovary syndrome, C-reactive protein levels and D-dimer, antithrombin III, activated protein C resistance, and activated partial thromboplastin time were unaffected by metformin treatment throughout pregnancy. Protein C levels increased slightly in the metformin group compared with the placebo group.
Fertility and sterility 04/2006; 85(3):770-4. · 3.97 Impact Factor
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ABSTRACT: Polycystic ovary syndrome is the most common endocrine condition in women of fertile age. The syndrome is associated with insulin resistance, hyperinsulinaemia and diabetes. This paper reviews the association between polycystic ovary syndrome and diabetes; implications for clinical practice are suggested.
The review is based on Medline searches, our own studies, and clinical experience.
Polycystic ovary syndrome is present in one third of women with type 1 diabetes and in almost half of all women with type 2 diabetes. In women with polycystic ovary syndrome, the prevalence of type 2 diabetes is considerably increased and gestational diabetes may occur in as many as 40%. In women with previous gestational diabetes, the risk of type 2 diabetes as well as polycystic ovarian syndrome is increased.
Women with polycystic ovary syndrome are at increased risk of developing type 2 diabetes and gestational diabetes and should be followed up accordingly. Pregnant women with polycystic ovary syndrome should have an oral glucose tolerance test as soon as the pregnancy has been confirmed. The procedure should be repeated at gestational weeks 20 and 32. Treatment with metformin should be initiated in women with type 2 diabetes who want to conceive. For the same reason metformin may also be initiated in women with type 1 diabetes.
Tidsskrift for den Norske laegeforening 11/2005; 125(19):2619-21.
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Fertility and sterility 06/2005; 83(5):1575-8. · 3.97 Impact Factor
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ABSTRACT: The aim was to investigate the clinical, biochemical and ultrasonographic characteristics of Scandinavian women with polycystic ovarian syndrome (PCOS), and to see whether there were any differences between eumenorrhoic and oligoamenorrhoic women.
Eighty women aged between 18 and 40 years with PCOS were investigated in a prospective study. The inclusion criteria were polycystic ovaries (PCO), body mass index (BMI) >25 kg/m(2) and at least one of the following: testosterone >2.5 nmol/L, sex hormone binding globulin (SHBG) <30 nmol/L, fasting C-peptide >1.0 nmol/L, oligoamenorrhea or hirsutism.
Eumenorrhoic and oligoamenorrhoic women with PCOS did not differ in age, age at menarche, blood pressure, BMI, free testosterone index (FTI), insulin C-peptide or fasting glucose. A thicker endometrium and a smaller ovarian volume were found in eumenorrhoic compared to oligoamenorrhoic patients. There was linear association between BMI and the number of diagnostic criteria met.
BMI was associated with the severity of the PCOS. There were no differences in basic clinical and biochemical parameters between eumenorrhoic and oligoamenorrhoic patients with PCOS.
Acta Obstetricia Et Gynecologica Scandinavica 05/2004; 83(5):482-6. · 1.77 Impact Factor
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ABSTRACT: Women with polycystic ovary syndrome treated with metformin and lifestyle advice were studied. Additional treatment with dexamethasone, but not with bromocriptine, further reduced circulating androgen levels.
Fertility and Sterility 03/2004; 81(2):459-62. · 3.56 Impact Factor
