Holistic approach to care for patients with endometriosis.

PURPOSE OF REVIEW: Endometriosis is a chronic, often debilitating, disease which is typically managed with surgery and hormonal medications. However, many patients feel they lack agency when managing endometriosis symptoms. The purpose of this review is to discuss the mental and physical management strategies, the long-term health consequences, and the role of a multidisciplinary team in the treatment of endometriosis. RECENT FINDINGS: Evidence is becoming more robust regarding the role of complementary care and physical activity in the management of endometriosis. Health risks such as infertility are well known and newer evidence is evolving regarding perinatal and cardiovascular health risks. There are also trends towards multiple specialist involvement in the care of endometriosis and the benefit of interdisciplinary collaboration. SUMMARY: Endometriosis is a frequently recurrent condition requiring not only meticulous medical and surgical care, but also coordinated longitudinal disease management and impact mitigation. Gynecologists should be aware of the short-term and long-term implications of the disease to empower patients on the management of their overall health.

AKAP13 Enhances CREB1 Activation by FSH in Granulosa Cells.

Granulosa cells (GCs) must respond appropriately to follicle-stimulating hormone (FSH) for proper follicle maturation. FSH activates protein kinase A (PKA) leading to phosphorylation of the cyclic AMP response element binding protein-1 (CREB1). We identified a unique A-kinase anchoring protein (AKAP13) containing a Rho guanine nucleotide exchange factor (RhoGEF) region that was induced in GCs during folliculogenesis. AKAPs are known to coordinate signaling cascades, and we sought to evaluate the role of AKAP13 in GCs in response to FSH. Aromatase reporter activity was increased in COV434 human GCs overexpressing AKAP13. Addition of FSH, or the PKA activator forskolin, significantly enhanced this activity by 1.5- to 2.5-fold, respectively (p < 0.001). Treatment with the PKA inhibitor H89 significantly reduced AKAP13-dependent activation of an aromatase reporter (p = 0.0067). AKAP13 physically interacted with CREB1 in co-immunoprecipitation experiments and increased the phosphorylation of CREB1. CREB1 phosphorylation increased after FSH treatment in a time-specific manner, and this effect was reduced by siRNA directed against AKAP13 (p = 0.05). CREB1 activation increased by 18.5-fold with co-expression of AKAP13 in the presence of FSH (p < 0.001). Aromatase reporter activity was reduced by inhibitors of the RhoGEF region, C3 transferase and A13, and greatly enhanced by the RhoGEF activator, A02. In primary murine and COV43 GCs, siRNA knockdown of Akap13/AKAP13 decreased aromatase and luteinizing hormone receptor transcripts in cells treated with FSH, compared with controls. Collectively, these findings suggest that AKAP13 may function as a scaffolding protein in FSH signal transduction via an interaction with CREB, resulting in phosphorylation of CREB.

Obstetrical outcomes are unchanged after hysteroscopic myomectomy in women with submucosal fibroids.

BACKGROUND: Previous studies have demonstrated increased rates of poor obstetrical outcomes including preterm delivery, placental abruption, and intrauterine growth restriction in women with uterine leiomyomas. Currently, preconception myomectomy has not been reported to improve pregnancy rates or pregnancy outcomes in women with subserosal leiomyomas, and the data remain inconclusive for intramural fibroids. Pregnancy rates have been found to improve after the removal of submucosal fibroids. However, the effect of preconception myomectomy for submucosal fibroids on birth outcomes has yet to be examined. OBJECTIVE: This study aimed to determine whether hysteroscopic excision of submucosal leiomyomas affects the rate of preterm delivery, among other obstetrical outcomes. STUDY DESIGN: We performed a retrospective case-control study of women who underwent hysteroscopic resection of leiomyomas (cases) and controls of women who had submucosal fibroids at the time of their first-trimester ultrasounds. Women were included if they delivered a nonanomalous fetus beyond 20 weeks' gestation. A total of 73 cases were identified and matched with 219 controls (case-to-control ratio, 1:3). Subsequently, owing to multiple-gestation pregnancy, 11 patients were excluded from the case population and 4 patients from the control group. The final analysis included 277 women-62 cases and 215 controls. Our primary outcome was preterm delivery before 37 weeks' gestation. Prespecified secondary outcomes of interest were preterm delivery before 34 weeks' gestation, placental abruption, fetal malpresentation, intrauterine growth restriction, and rate of cesarean delivery. Data analysis was performed using univariate and multivariate statistics. RESULTS: Cases and controls were similar with respect to age, race, body mass index, and mode of delivery. Cases were more likely to be primiparous (66% cases [42 of 62] vs 37% controls [80 of 215]; P=.00) and use assisted reproductive technology to conceive (22.6% cases [14 of 62] vs 7.0% controls [15 of 215]; P<.001). No differences were found in the rate of preterm delivery at <37 weeks' gestation (12.9% cases [8 of 62] vs 13.5% controls [29 of 215]; P=.89), preterm delivery at <34 weeks' gestation (4.84% cases [3 of 62] vs 6.97% controls [15 of 215]; P=.77), or other obstetrical outcomes. CONCLUSION: Overall, women with submucosal uterine leiomyomas who undergo hysteroscopic removal have similar birth outcomes to those who do not.