What is the best drug treatment for premenopausal women with bleeding irregularities using the levonorgestrel-releasing intrauterine system? A systematic review.

OBJECTIVE: Up to 60% of women discontinue using the levonorgestrel-releasing intrauterine system (LNG-IUS) within 5 years because of bleeding irregularities, pain and/or systemic progestogenic adverse effects. The aim of the study was to assess treatment options for bleeding irregularities in women using the 52 mg LNG-IUS. METHODS: Database searches of Medline, Embase/Ovid and the Cochrane Library were carried out, and journals were searched by hand, for relevant studies published from database inception to March 2020. Inclusion criteria were randomised controlled trials (RCTs), prospective cohort studies and case-control studies of premenopausal women using the LNG-IUS and receiving medical treatment for bleeding irregularities. Screening, data extraction and quality assessment of retrieved articles were carried out independently by two pairs of reviewers. The primary outcome was the reduction of bleeding/spotting days. RESULTS: Of the 3061 studies identified, eight met our inclusion criteria: six RCTs and two prospective cohort studies. The eight studies enrolled a total of 677 women who were treated with tamoxifen, mifepristone, ulipristal acetate, naproxen, oestradiol, mefenamic acid, tranexamic acid or the progesterone receptor modulator CDB 2914. The results of our analysis indicated that naproxen may be effective for the prophylactic treatment of bleeding immediately (<12 weeks) after LNG-IUS insertion (high level of evidence). Oestradiol may be effective in treating ongoing bleeding irregularities >6 months after insertion (low level of evidence). CONCLUSION: Evidence for the medical treatment of (ongoing) bleeding irregularities during use of the LNG-IUS is lacking and more research is needed on the topic.

Oestrogen modulates cardiac ischaemic remodelling through oestrogen receptor-specific mechanisms.

AIM: Observational and clinical studies suggest different responses upon sex hormone replacement therapy in ischaemic heart disease. Few studies, however, have examined the impact of oestrogen receptor-dependent mechanisms on the extent of injury after myocardial infarction (MI). Therefore, we set out to evaluate the effect of oestrogen (E2) replacement on infarct size and remodelling, and the respective role of the oestrogen receptors (ER)alpha and -beta in this process, using ERalpha- and ERbeta-deficient mice. METHODS: Wild type (WT) (ERalpha(+/+) and ERbeta(+/+)), ERalpha-deficient (ERalpha(-/-)) and ERbeta-deficient (ERbeta(-/-)) mice were ovariectomized and subsequently supplemented with E2 or placebo using subcutaneous 60-day release pellets. MI was induced by left coronary artery ligation. Two weeks following MI, haemodynamic function was assessed and infarct size was determined. RESULTS: There was no significant difference in infarct size between E2- or placebo-treated WT (ERalpha(+/+) and ERbeta(+/+)) mice. Surprisingly, E2 treatment did result in smaller infarct sizes in ERalpha(-/-) mice, but increased the infarct size in ERbeta(-/-) mice. Increase of the left ventricular mass post-MI was significantly larger in the E2-treated ERalpha(-/-) animals compared with placebo-treated animals. E2 treatment also significantly increased post-MI mortality in ERalpha(+/+), ERbeta(+/+) and ERalpha(-/-) animals, but not in ERbeta(-/-) mice. CONCLUSIONS: Although E2 modulates the infarct size in ERalpha(-/-), it also appears to be responsible for the higher mortality following MI. ERbeta appears to be the receptor involved in the modulating effects of E2 in the infarcted heart.

[Polychlorodibenzo-p-dioxins (author's transl)]. / Les polychloro dibenzo-p-dioxines

Polychlorodibenzo-p-dioxins (chlorodioxins) appear most frequently by heating of chlorophenols in alkaline solution specially when producing organic derivatives. Consequently chlorodioxins may contaminate several industrial chemical products largely used, for instance, as pesticides. Occasionally, chlorodioxins are also synthesized from chlorophenols or their derivatives in situ during industrial processes. Chlorodioxins are the cause of chloracne and chick edema which killed thousands of broiler chickens in the U.S.A. Furthermore chlorodioxins seem to be foetotoxic possible even for man. The present paper is the first part of our work. It is a review of the chemical and toxicological properties of chlorodioxins. We hope to publish later a review of analytical methods and the results of our analyses.