Phthalates and polycystic ovary syndrome - Systematic literature review.

Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in women, may involve both environmental and genetic factors. One potential environmental factor of concern is exposure to phthalates and other endocrine disrupting chemicals many of which have adverse effects on the female reproductive system. The aim of this systematic review was to evaluate possible association between prenatal phthalate exposure and PCOS. Six databases were searched for relevant human studies. Inclusion criteria were female human population diagnosed with PCOS and exposed during any lifestage to any phthalate or phthalate metabolite through oral, dermal, inhalation, or intravenous route. Search results were screened for relevance, and studies that met the inclusion criteria were evaluated for study quality using Joanna Briggs Institute (JBI) critical appraisal tools. The systematic literature search yielded seven articles, six case-control studies and one cohort study. Three studies found a significant positive association, two studies found a significant negative association, and two studies found no association between phthalate exposure and the incidence of PCOS. Even though studies found no consistent pattern on association with phthalates and PCOS, the results of analyzed studies did not exclude possible effects of phthalates on the female reproductive and metabolic system. Some of the factors in study design such as recruiting participants from IVF clinics and young age of participants may have biased the results. Further studies with more careful study design and longer follow-up time are needed to bring more reliable information about the role of phthalates in onset of PCOS.

Increased risk of preeclampsia after use of paracetamol during pregnancy - causal or coincidence?

BACKGROUND: The maternal use of paracetamol during pregnancy has been associated with the development of preeclampsia. This study aims to clarify whether the connection is causal or whether it is due to reverse causation. METHODS: This study is a continuation of the retrospective case cohort study examining 2,508 pregnant women using a variety of drugs and the development of preeclampsia (1,252 women with preeclampsia and 1,256 controls). For the purposes of this study, more precise data was collected from several hospital databases of the women among this cohort who had reported taking paracetamol during pregnancy (indications, gestational period etc.); this was evaluated in association with the development of preeclampsia. RESULTS: 5.5% (100 cases and 37 controls) of all the study population (2,508) had clearly reported paracetamol use. Women with preeclampsia had used significantly more often paracetamol during pregnancy compared to controls (cases 8.0%, controls 2.9%, p < 0.001). The difference was most evident in the third trimester (after the 29th GW) and the use of paracetamol was associated with both mild and severe preeclampsia. Headache and "general pain" were the most common indications for medication among all paracetamol users. CONCLUSIONS: The use of paracetamol in the third trimester of pregnancy was associated with preeclampsia. This observation indicates that association between paracetamol use and preeclampsia is probably due to reverse causation, i.e. women with preeclampsia experience more headaches due to preeclampsia symptoms since this association was not detected with the use of paracetamol in earlier stages of pregnancy.

Hypothyroidism and the increased risk of preeclampsia - interpretative factors?

OBJECTIVE: To evaluate the causes behind the association between hypothyroidism and the risk of preeclampsia. METHODS: Checking of individual hospital and birth records from 149 levothyroxine users among 2,508 women in the preeclampsia case-control study (2002-2016). RESULTS: There were significant association between levothyroxine medication and preeclampsia (OR 1.48, 95th CI 1.06-2.07; p ≤ 0.022). The presence of comorbid diseases was associated with a significantly higher risk for the development of preeclampsia in women using levothyroxine. CONCLUSION: Levothyroxine use during pregnancy was associated with 1.5-times higher risk for preeclampsia, but it is also linked to the other comorbid risk factors.

Activities of metabolizing enzymes in human placenta.

In addition to the transfer across the placenta, placenta displays hormonal and xenobiotic metabolism, as well as enzymatic defense against oxidative stress. We analyzed aromatase (CYP19A1), uridine 5'-diphospho-glucuronyltransferase (UGT), glutathione-S-transferase (GST) and catalase (CAT) activities in over 70 placentas from nonsmokers stored at -80 °C from former perfusion studies. A wide interindividual variation in all activities was found. Longterm storage at -80 °C did not affect the activities. Ethoxyresorufin-O-deethylase (EROD, CYP1A1) was not detected in any of the studied placentas perfused with chemicals. Several compounds in placental perfusion changed statistically significantly the enzyme activities in placental tissue. Melamine and nicotine increased CYP19A1, melamine increased UGT and GST, PhIP with ethanol decreased CYP19A1 and increased GST, and PhIP with buprenorphine decreased CAT. Antipyrine in 100 µg/ml also changed the studied enzyme activities, but not statistically significantly. Because antipyrine is a reference compound in placental perfusions, its potential effects must be taken into account in human placental perfusion. Enzyme activities deserve further studies as biomarkers of placental toxicity. Finally, enzyme activities deserve further studies as biomarkers of placental toxicity.

Maternal use of drugs and preeclampsia.

AIMS: The aim was to compare and describe maternal use of drugs between women with preeclampsia and controls and to estimate the possible association with preeclampsia. METHODS: The study cohort was collected from the Kuopio University Hospital Birth Register, which includes information about all women who gave birth in Kuopio University Hospital during the years 2002-2016, including information from approximately 36 000 parturients, of whom 1252 had preeclampsia. Maternal use of 16 groups of drugs during pregnancy was analysed from all women with preeclampsia and 1256 controls. RESULTS: Every second woman had used at least 1 drug during pregnancy but those with preeclampsia had used significantly more than the controls (cases 59.5% vs controls 35.5%; p < 0.001). In both study groups, the most commonly used drugs were antibiotics (cases 19.5%, controls 17.0%), antihypertensives (cases 29.0%, controls 7.6%) and paracetamol (cases 13.1%, controls 5.9%). Women with preeclampsia had used significantly more benzodiazepines, paracetamol, antihypertensives and acid-suppressive drugs than the women in the control group (p < 0.05). CONCLUSIONS: Women with preeclampsia were more likely to use medicines during pregnancy. While the association between benzodiazepines, antihypertensives and acid-suppressive drugs and preeclampsia may be explained by reverse causation, the association of paracetamol with preeclampsia remains to be clarified. Because paracetamol is a frequently used drug, more information about its safety during pregnancy including its role in preeclampsia is urgently needed.