Thromboembolic complications of hormonal therapy in women. Position of cardiologist

Thromboembolic complications is a frequent cause of acute cardiovascular events, disability and mortality. Among the factors that increase their risk in the female population using of medications, containing sex hormones is of high significance. In oral contraceptives the main — contraceptive activity belongs to gestagen, while estrogen performs an auxiliary function of menstrual cycle control. In medications used for therapy during menopause the main active substance is estrogen. Progestin provides prevention of endometrial hyperplasia. Despite the intensive search for optimal effective and safe schemes of combined hormonal drugs, the risk of thrombotic complications in patients using them both for therapeutic purposes and as contraception remains high. The article provides clinical observations illustrating the administration of hormonal therapy to women is reasonable to be discussed and agreed with cardiologists and/or general practitioners, and the patients would be informed about possible cardiovascular complications of such therapy for an adequate selfcontrol.

Development of multipurpose technologies products for pregnancy and STI prevention: update on polyphenylene carboxymethylene MPT gel development†

Current modern contraceptives rely heavily on the use of hormones. These birth control drug products, including pills, patches, injections, and IUDS, have been extremely beneficial to millions of women and their families over the past 50 years. But a surprisingly high number of women abandon such modern methods, many because they cannot tolerate the side effects and others because they have medical issues for which hormonal methods are contraindicated. In addition, modern hormonal methods are simply not available to many women. The extent of this problem is steadily becoming more apparent. We present the case for developing simple nonhormonal vaginal products that women can use when needed, ideal products that are multipurpose and offer both contraception and sexually transmitted disease protection. Gel-based vaginal products are particularly well suited for this purpose. Gels are easy to use, highly acceptable to many women, and can be safely formulated to enhance natural vaginal defenses against infection. However, the development of a new chemical entity for this application faces significant technical and regulatory hurdles. These challenges and our solutions are described for polyphenylene carboxymethylene (PPCM), a novel topical drug in a vaginal gel nearing human clinical trials. We have advanced PPCM from benchtop to IND-enabling studies and provide a brief description of the complex development process. We also describe a simple lab assay which can be used as a biomarker for contraceptive activity to enable pharmacodynamic studies in vaginal contraceptive development, both preclinically and in early human clinical trials.

Quantitative Evaluation of Various Preparations and Extracts of the Male Contraceptive Justicia gendarussa and Identification of a New Aminobenzyl Derivative

Justicia gendarussa is a medicinal plant found in different regions of Indonesia and used in decoctions by Papuan tribes to reduce male fertility. An enriched ethanolic extract of this plant has been used in the frame of clinical trials in Indonesia to evaluate its male contraceptive activity. Previous studies have indicated that the flavonoid gendarusin A may have a role in the male contraception properties of this plant. In addition, the level of aminobenzyl derivatives was lowered as a safety precaution. In order to obtain a comprehensive chemical profile of the methanolic plant extract, it was analysed by HPLC-PDA-ESI-MS and UHPLC-TOF-HRMS. The same method was also applied to profile extracts of the same plant material from different Indonesian regions, a water decoction used traditionally, and the enriched extract used in clinical trials. This allowed for the dereplication of all previously known flavonoids and newly reported amides, and permitted highlighting the presence of the potentially new aminobenzyl derivative. Targeted isolation of this new amide was performed using medium-pressure liquid chromatography. NMR and HRMS allowed for the establishment of the identity of the novel compound. The same procedure was used to obtain pure standards for quantitative studies. Quantitation of the major compounds was performed for different extracts using HPLC-UV. Significant differences were observed between the samples. Although gendarusin A was the main compound in all samples, it occurred in different amounts in the batches of dried material obtained from different Indonesian regions. The enriched extract contained mainly gendarusin A, as did the traditional decoction, but the level of the aminobenzyl derivatives was significantly lower.

Synthesis, Cytotoxic and Contraceptive Activity of 6,8,9-Trihydroxy-2-methyl-2H-naphtho[2,3-b]pyran-5,10-dione, a Pigment of Echinothrix diadema, and its Analogs

6,8,9-Trihydroxy-2-methyl-2 H-naphtho[2,3- b]pyran-5,10-dion, a pigment of the sea urchin Echinothrix diadema, and six analogs were synthesized. The cytotoxic activity and contraceptive properties of the synthesized pyranonaphthazarins have been investigated using the sperm and eggs of the sea urchin Strongylocentrotus intermedius.