Postmenopausal Vaginal Microbiome and Microbiota

The ovulatory cycle has a significant influence on the microbial composition, according to the action of estrogen and progesterone on the stratified squamous epithelium, due to an increase in epithelial thickness, glycogen deposition, and influence on local immunology. The 16S rRNA gene amplification and pyrosequencing study demonstrated that healthy women have community state types (CST), classified as; type “L,” with a predominance of Lactobacillus crispatus, type II, with a predominance of Lactobacillus gasseri, type III, where Lactobacillus iners predominates, and type V with a predominance of Lactobacillus jensenii. Type IV does not identify lactobacilli but a heterogeneous population of bacteria. There seems to be a relationship between increased vaginal bacterial diversity and poverty of lactobacilli with the complaining of vaginal dryness. With menopause, there appears to be a reduction in lactobacilli associated with higher serum levels of follicle-stimulating hormone (FSH) and lower estrogen levels. The evaluation of Gram-stained vaginal smears in postmenopause women must take into account the clinical-laboratory correlation. We should observe two meanly possibilities, atrophy with few bacterial morphotypes, without inflammatory, infiltrate (atrophy without inflammation), and atrophy with evident inflammatory infiltrate (atrophy with inflammation or atrophic vaginitis). The relationship between the microbiome and postmenopausal vulvovaginal symptoms seems to be related to the bacterial vaginal population. However, more robust studies are needed to confirm this impression.

The Sexual and Reproductive Health Context of an Internally Displaced Persons' Camp in Northeastern Nigeria: Narratives of Girls and Young Women

In humanitarian settings, ~35 million girls and young women of reproductive age (15–24) are in urgent need of sexual and reproductive health (SRH) information and services. Young women and girls in humanitarian contexts are particularly vulnerable to unwanted pregnancies, unsafe abortion, gender-based violence, and early and forced marriage. We sought to understand girls' and young women's experiences with unwanted pregnancy, abortion, contraception, sexually transmitted infections (STIs), gender-based violence (GBV), and forced marriage in an IDP camp in Northeastern Nigeria. We conducted 25 in-depth interviews with girls aged 15–19 (N = 13; 8 single and 5 married) and young women aged 20–24 (N = 12; 3 single and 9 married). All interviews were audiotaped, transcribed, translated, computer recorded and coded for analysis. The participants in our study fled from and witnessed violence to arrive in the IDP camp with little material support. Lack of necessities, especially food, has driven many to sex in exchange for goods or into forced marriages. This, in turn, leads to increased unwanted pregnancies and unsafe abortions. Participants had limited knowledge about contraception, and some information about SRH services available in the camp, but overall, knowledge and utilization of SRH services was low.

Mechanisms of Scarless Repair at Time of Menstruation: Insights From Mouse Models

The human endometrium is a remarkable tissue which may experience up to 400 cycles of hormone-driven proliferation, differentiation and breakdown during a woman's reproductive lifetime. During menstruation, when the luminal portion of tissue breaks down, it resembles a bloody wound with piecemeal shedding, exposure of underlying stroma and a strong inflammatory reaction. In the absence of pathology within a few days the integrity of the tissue is restored without formation of a scar and the endometrium is able to respond appropriately to subsequent endocrine signals in preparation for establishment of pregnancy if fertilization occurs. Understanding mechanisms regulating scarless repair of the endometrium is important both for design of therapies which can treat conditions where this is aberrant (heavy menstrual bleeding, fibroids, endometriosis, Asherman's syndrome) as well as to provide new information that might allow us to reduce fibrosis and scar formation in other tissues. Menstruation only occurs naturally in species that exhibit spontaneous stromal cell decidualization during the fertile cycle such as primates (including women) and the Spiny mouse. To take advantage of genetic models and detailed time course analysis, mouse models of endometrial shedding/repair involving hormonal manipulation, artificial induction of decidualization and hormone withdrawal have been developed and refined. These models are useful in modeling dynamic changes across the time course of repair and have recapitulated key features of endometrial repair in women including local hypoxia and immune cell recruitment. In this review we will consider the evidence that scarless repair of endometrial tissue involves changes in stromal cell function including mesenchyme to epithelial transition, epithelial cell proliferation and multiple populations of immune cells. Processes contributing to endometrial fibrosis (Asherman's syndrome) as well as scarless repair of other tissues including skin and oral mucosa are compared to that of menstrual repair.

Genetic Regulation of Transcription in the Endometrium in Health and Disease

The endometrium is a complex and dynamic tissue essential for fertility and implicated in many reproductive disorders. The tissue consists of glandular epithelium and vascularised stroma and is unique because it is constantly shed and regrown with each menstrual cycle, generating up to 10 mm of new mucosa. Consequently, there are marked changes in cell composition and gene expression across the menstrual cycle. Recent evidence shows expression of many genes is influenced by genetic variation between individuals. We and others have reported evidence for genetic effects on hundreds of genes in endometrium. The genetic factors influencing endometrial gene expression are highly correlated with the genetic effects on expression in other reproductive (e.g., in uterus and ovary) and digestive tissues (e.g., salivary gland and stomach), supporting a shared genetic regulation of gene expression in biologically similar tissues. There is also increasing evidence for cell specific genetic effects for some genes. Sample size for studies in endometrium are modest and results from the larger studies of gene expression in blood report genetic effects for a much higher proportion of genes than currently reported for endometrium. There is also emerging evidence for the importance of genetic variation on RNA splicing. Gene mapping studies for common disease, including diseases associated with endometrium, show most variation maps to intergenic regulatory regions. It is likely that genetic risk factors for disease function through modifying the program of cell specific gene expression. The emerging evidence from our gene mapping studies coupled with tissue specific studies, and the GTEx, eQTLGen and EpiMap projects, show we need to expand our understanding of the complex regulation of gene expression. These data also help to link disease genetic risk factors to specific target genes. Combining our data on genetic regulation of gene expression in endometrium, and cell types within the endometrium with gene mapping data for endometriosis and related diseases is beginning to uncover the specific genes and pathways responsible for increased risk of these diseases.

Obstetric Outcome After Surgical Treatment of Endometriosis: A Review of the Literature

A diagnosis of endometriosis is associated with increased risks of adverse pregnancy outcomes including placenta praevia and preterm birth. Some studies have also suggested associations with gestational hypertension, foetal growth restriction, gestational diabetes, perinatal death, and obstetric haemorrhage. This review aims to assess the impact of pre-pregnancy surgical treatment of endometriosis on future obstetric outcomes. A search of the Medline, Embase and PubMed electronic databases was performed to identify studies reporting pre-pregnancy surgery for endometriosis and subsequent pregnancy outcome compared to controls with unresected endometriosis. Three studies met the inclusion criteria. The studies were heterogenous in design, definition of study groups and outcome measures. All three studies were judged at critical risk of bias. Pre-pregnancy excision of endometriosis was associated with an increased risk of caesarean section in one of two studies, OR 1.72 (95% CI 1.59–1.86) and OR 1.79 (95% CI 0.69–4.64). Placenta praevia rates were also increased in one of two studies OR 2.83 (95% CI 0.56–12.31) and OR 2.04 (95% CI 1.66–2.52). One study found increased risks of preterm birth, small for gestational age, gestational hypertension, and antepartum and postpartum haemorrhage (all p < 0.05) with pre-pregnancy excision of endometriosis. There is insufficient evidence examining the role of pre-pregnancy endometriosis surgery in ameliorating adverse pregnancy outcomes, and thus reliable conclusions cannot be drawn. Prospectively designed studies are needed to assess the relationship between surgical treatments for endometriosis and obstetric outcome and examine potential confounders such as comorbid adenomyosis and infertility.

Considerations in Adolescent Use of the Etonogestrel Subdermal Implant: A Cohort Study

Objectives: To describe bleeding patterns and other side effects in adolescent implant users and characterize their impact on early discontinuation of the implant.Study Design: This is a retrospective cohort study of female patients under 18 years who had an implant placed from 2013 to 2018. Data were collected on demographics, medical history, and side effects.Results: Of 212 adolescents, the average age at insertion was 16 years and 84% desired placement for contraception. Common side effects included AUB (80%), mood changes (10%), and perceived weight gain (9%). Most (76%) used the implant for at least 12 months. Average time to removal was 22.1 months (SD 13.0 months) and this did not depend on presence of side effects. Twenty-seven percent of teens were able to achieve amenorrhea. Adolescents with frequent or prolonged bleeding were more likely to have implant removal prior to 12 months than those with other bleeding patterns (p = 0.003). Early removal was also more common in girls reporting weight or mood issues than those who did not (p < 0.001 and p = 0.045, respectively). BMI increased in 64% of adolescents. Average percentage change in BMI was 3.2% (0.87 kg/m2). There was no difference in baseline use of any mood-modulating medications in patients who did and did not complain of mood side effects following implant placement (p = 0.801).Conclusion: Characterization of bleeding patterns following implant placement in adolescents have not previously been reported. Prolonged or heavy bleeding, mood issues, and perceived weight gain were associated with earlier removal of the implant. A relatively small number had early removal of the implant due to weight or mood complaints. Therefore, a history of obesity, depression, or other mood disorders should not be a deterrent to implant placement.

The Role of Decidual Subpopulations in Implantation, Menstruation and Miscarriage

In each menstrual cycle, the endometrium becomes receptive to embryo implantation while preparing for tissue breakdown and repair. Both pregnancy and menstruation are dependent on spontaneous decidualization of endometrial stromal cells, a progesterone-dependent process that follows rapid, oestrogen-dependent proliferation. During the implantation window, stromal cells mount an acute stress response, which leads to the emergence of functionally distinct decidual subsets, reflecting the level of replication stress incurred during the preceding proliferative phase. Progesterone-dependent, anti-inflammatory decidual cells (DeC) form a robust matrix that accommodates the conceptus whereas pro-inflammatory, progesterone-resistant stressed and senescent decidual cells (senDeC) control tissue remodelling and breakdown. To execute these functions, each decidual subset engages innate immune cells: DeC partner with uterine natural killer (uNK) cells to eliminate senDeC, while senDeC co-opt neutrophils and macrophages to assist with tissue breakdown and repair. Thus, successful transformation of cycling endometrium into the decidua of pregnancy not only requires continuous progesterone signalling but dominance of DeC over senDeC, aided by recruitment and differentiation of circulating NK cells and bone marrow-derived decidual progenitors. We discuss how the frequency of cycles resulting in imbalanced decidual subpopulations may determine the recurrence risk of miscarriage and highlight emerging therapeutic strategies.

Use of Moisturizers and Lubricants for Vulvovaginal Atrophy

The estrogen decrease in postmenopausal women results in functional and anatomical changes in the genitourinary tract. The most prevalent and bothersome symptoms are vaginal dryness, dyspareunia, and reduced lubrication, which can significantly affect the quality of life of these women, principally those who are sexually active. Hormonal therapy with local estrogens is generally considered the “gold standard.” However, there are cases in which there are clinical concerns about its use or women opt for non-hormonal options. Thus, safe and effective non-hormonal options are needed to improve symptoms in these women. Moisturizers and lubricants are first-line therapy for breast cancer survivors.