Objective: Endometriosis affects up to 10% of women of reproductive age, and the main goal of treatment is to relieve symptoms. Progestins have been the mainstay of endometriosis suppression, of which dienogest has become an important option in many parts of the world. This is an expert literature review, with recommendations on the use of dienogest in the context of various clinical considerations when treating endometriosis. Methods: A search of PubMed was conducted for papers published between 2007 and 2019 on the use of dienogest in endometriosis. Experts reviewed these and included those they considered most relevant in clinical practice, according to their own clinical experience. Results: Evidence regarding the long-term use (>15 months) of dienogest for the management of endometriosis is presented, with experts concluding that the efficacy of dienogest should be assessed primarily on its impact on pain and quality of life. Fertility preservation, the option to avoid or delay surgery, and managing bleeding irregularities that can occur with this treatment are also considered. Counseling women on potential bleeding risks before starting treatment may be helpful, and evidence suggests that few women discontinue treatment for this reason, with the benefits of treatment outweighing any impact of bleeding irregularities. Conclusions: Overall, the evidence demonstrates that dienogest offers an effective and tolerable alternative or adjunct to surgery and provides many advantages over combined hormonal contraceptives for the treatment of endometriosis. It is important that treatment guidelines are followed and care is tailored to the woman’s individual needs and desires.

Background: Nutrition status prior to conception and during pregnancy and infancy seems to have an influence on the disease risk in adulthood (early nutrition/developmental programming). We aimed to review the current knowledge on the role of micronutrients in early nutrition programming and its implications for healthcare. Summary of Findings: Globally and even in high-income countries where a balanced diet is generally accessible, an inadequate maternal micronutrient status is common. This may induce health problems in the mother and foetus/newborn both immediately and in later life. Pregnant women and those who may become pregnant should aim to achieve a satisfactory micronutrient status from a well-balanced diet, and where necessary from additional supplements. Key Messages: We emphasise the need for a call to action for healthcare providers and policymakers to better educate women of child-bearing age regarding the short- and long-term benefits of an appropriate micronutrient status. The role of micronutrient status in early nutrition programming needs to be emphasized more to address the still limited awareness of the potential long-term health repercussions of suboptimal micronutrient supply during pregnancy.

We review recent studies dealing with the molecular genetics and basic results of omics analysis of uterine leiomyoma (LM)—a common benign muscle tumor of the uterus. Whole genome studies of LM resulted in the discovery of many new gene nets and biological pathways, including its origin, transcriptomic, and epigenetic profiles, as well as the impact of the inter-cell matrix in LM growth and involvement of microRNA in its regulation. New data on somatic cell mutations ultimately involved in the origin, distribution and growth of LM are reviewed. Putative identification of LM progenitor SC (stem cells) giving rise to maternal fibroid nodes and junctional zones provide a new clue for hypotheses on the pathogenomics of LM. The reviewed data are consistent with at least two different but probably intimately interacted molecular mechanisms of LM. One of them (the genetic hypothesis) is focused primarily on the MED12 gene mutations and suggests its onset in the side population of embryonic myoblasts of the female reproductive system, which later gave rise to multiple small and medium fibroids. The single and usually large-size fibroids are induced by predominantly epigenetic disorders in LM SC, provoked by enhanced expression of the HMGA2 gene caused by its hypomethylation and epigenetic deregulation enhanced by hypoxia, muscle tension, or chromosome instability/aberrations. The pathogenomics of both genetic and epigenetic programs of LM with many peculiarities at the beginning later became rather similar and partly overlapped due to the proximity of their gene nets and epigenetic landscape. Pathogenomic studies of LM open ways for elaboration of novel strategies of prevention and treatment of this common disease.

For over 100 years, endometriosis, as a chronic, estrogen-dependent, inflammatory, heritable disease affecting approximately 5–10% of women in reproductive age has been the focus of clinicians and scientists. In spite of numerous environmental, genetic, epigenetic, endocrine, and immunological studies, our knowledge of endometriosis is still fragmentary, and its precise pathophysiology and pathogenomics remain a mystery. The implementation of new technologies has provided tremendous progress in understanding the many intrinsic molecular mechanisms in the development of endometriosis, with progenitor and stem cells (SCs) of the eutopic endometrium as the starting players and endometriotic lesions as the final pathomorphological trait. Novel data on the molecular, genetic, and epigenetic mechanisms of the disease are briefly outlined. We hypothesize the existence of an endometriosis development genetic program (EMDP) that governs the origin of endometrium stem cells programmed for endometriosis (1), their transition (metaplasia) into mesenchymal SCs (2), and their invasion of the peritoneum and progression to endometriotic lesions (3). The pros and cons of the recent unifying theory of endometriosis are also discussed. Complex genomic and epigenetic interactions at different stages of the endometriosis process result in different forms of the disease, with specific features and clinical manifestations. The significance of the EMDP in elaborating a new strategy for endometriosis prediction, prevention, and treatment is discussed.

To compare the effectiveness of two different treatment regimens of dydrogesterone in the management of endometriosis-related chronic pelvic pain. Observational, prospective cohort study over six months. Twenty gynecology clinics in the Russian Federation. Three hundred fifty women from 18 to 45 years of age with endometriosis and chronic pelvic pain with or without dysmenorrhea. Dydrogesterone 10 mg 2 or 3 times daily, either between the 5th and 25th days of the menstrual cycle (prolonged cyclical treatment regimen) or continuously (continuous treatment regimen). For all patients, the data cutoff was at six months of treatment. Intensity of chronic pelvic pain on the 11-point numerical rating scale (after 6 months). A marked reduction in chronic pelvic pain was observed with both the prolonged cyclical and continuous treatment regimens (mean ± standard deviation change from baseline -3.3 ± 2.2 and -3.0 ± 2.2, respectively), with no significant difference between the two groups. With both regimens, patients experienced significant improvements in the intensity of chronic pelvic pain, number of days in which analgesics were required, severity of dysmenorrhea, sexual well-being, and health-related quality-of-life parameters. A favorable safety profile of dydrogesterone was confirmed, and no serious adverse drug reactions were reported during the study. Prolonged cyclical and continuous treatment regimens of dydrogesterone therapy both demonstrated a pronounced and similar reduction in the severity of chronic pelvic pain and dysmenorrhea and led to marked improvements in all study parameters related to quality of life and sexual well-being. NCT03690765.