Polycystic ovary syndrome - Long-term metabolic and respiratory health
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PCOS is an endocrine disorder affecting 10-15% of reproductive-aged women. Women with PCOS seek health-care most commonly due to irregular periods and/or challenges related to fertility and pregnancy. Treatment options are established addressing the core symptoms in both the pregnant and non-pregnant state in women with PCOS. Markers indicative of inferior metabolic health are increased in women with PCOS already in the reproductive period. Long-term implications of PCOS and associated conditions are areas where knowledge is limited. Both the development of the disorder and many of the PCOS-associated traits are underpinned by derangement in glucose-homeostasis and decreased insulin sensitivity. Initiation of successful lactation after pregnancy, in which the hormone prolactin plays a crucial role, also seems to be related to metabolic health. Impaired glucose-regulation are associated with decreased lung function. Common developmental traits are seen in asthma and decreased respiratory function in comparison to PCOS. In epidemiological studies, the prevalence of asthma is increased in women with PCOS. Metformin is an insulin sensitizer lowering hepatic glucose-output. Metformin is used in PCOS to treat both reproductive aspects of PCOS and the disorder itself. Metformin is increasingly used in gestational diabetes and to reduce pregnancy-complications in women with PCOS. Gestational weight-gain above established recommendations may have long-term consequences for maternal metabolic health. Pregnancy itself is a metabolic stress-test of maternal health in which insulin resistance is increased. Women with PCOS who used metformin in pregnancy had less weight-gain in pregnancy. Long-term follow-up of women with PCOS after metformin in pregnancy has not been carried out previously. Aim: The aim of the project was to investigate if metformin in pregnancy modified long-term metabolic health in women with PCOS. We also explored prolactin and breast increment in pregnancy in association with metabolic health and studied respiratory health in women with PCOS compared to healthy controls. Methods: We invited participants from two double-blinded randomized controlled trials (one pilot study and the PregMet study) to a follow-up study. Women with PCOS were randomized to metformin or placebo in pregnancy. In the first paper, long-term metabolic profile at 8 years follow-up was investigated. Weight-gain from first trimester of pregnancy until follow-up was our main end-point. The second paper explored how prolactin associated with markers of metabolic health, both in pregnancy and at follow-up. Respiratory health in women with PCOS was the topic of the third paper. We explored the prevalence of respiratory symptoms, asthma, atopy and in addition a spirometry was performed. Women with PCOS were matched (1:3) with healthy control-women on age and smoking-status from a population-based study (the HUNT-study). Results: In women with PCOS, metformin in pregnancy did not influence weight-gain form inclusion in the PregMet study until follow-up. Body composition and metabolic health at follow-up did not differ between the metformin and placebo groups. Prolactin increase from first to third trimester of pregnancy correlated to BMI and systolic blood pressure in third trimester of pregnancy in women with PCOS; the higher increase of prolactin in pregnancy, the lower BMI and systolic blood pressure in late pregnancy. Prolactin increase in pregnancy correlated positively to breast increment in pregnancy. Further, women with high prolactin increase had lower f-glucose and f-insulin in gestational week 32 of pregnancy compared to women with low prolactin increase. Inferior metabolic profile and body composition were described in follow-up among women who reported lack of breast increase during pregnancy. Prolactin in third trimester and increase of prolactin in pregnancy was comparable in metformin and placebo-treated women. Women with PCOS had more asthma and inferior respiratory function compared to controls. Women with PCOS seemed to be particularly prone to develop asthma in the peripubertal period (11-15 years) compared to controls. Metformin in pregnancy did not seem to consistently affect the prevalence of asthma, asthma symptoms or respiratory function at follow-up in women with PCOS. Increased knowledge and awareness of PCOS-associated conditions are necessary to optimize the long-term health in these women. Metformin in pregnancy does not improve long-term health in women with PCOS.