The effects of postmenopausal hormone treatment on cognitive outcomes are inconsistent in the literature. Emerging evidence suggests that cognitive effects are influenced by specific hormone formulations, and that progesterone is more likely to be associated with positive outcomes than synthetic progestin. There are very few studies of unopposed progesterone in postmenopausal women, and none that use functional neuroimaging, a sensitive measure of neurobiological function. In this study of 29 recently postmenopausal women, we used functional MRI and neuropsychological measures to separately assess the effects of estrogen or progesterone treatment on visual and verbal cognitive function. Women were randomized to receive 90 days of either estradiol or progesterone counterbalanced with placebo. After each treatment arm, women were given a battery of verbal and visual cognitive function and working memory tests, and underwent functional MRI including verbal processing and visual working memory tasks. We found that both estradiol and progesterone were associated with changes in activation patterns during verbal processing. Compared to placebo, women receiving estradiol treatment had greater activation in the left prefrontal cortex, a region associated with verbal processing and encoding. Progesterone was associated with changes in regional brain activation patterns during a visual memory task, with greater activation in the left prefrontal cortex and right hippocampus compared to placebo. Both treatments were associated with a statistically nonsignificant increase in number of words remembered following the verbal task performed during the fMRI scanning session, while only progesterone was associated with improved neuropsychological measures of verbal working memory compared to placebo. These results point to potential cognitive benefits of both estrogen and progesterone.
Female reproductive tract pathologies arise largely from dysregulation of estrogen and progesterone receptor signaling leading to aberrant cell proliferation, survival and differentiation. The signaling pathways orchestrated by these nuclear receptors are complex, require the participation of many nuclear proteins serving as key binding partners or targets and involve a range of paracrine and autocrine regulatory circuits. Members of the Krüppel-like family of transcription factors are ubiquitously expressed in reproductive tissues and have been increasingly implicated as critical co-regulators and integrators of steroid hormone actions. Here we explore the involvement of KLF family members in uterine pathology, describe their currently known molecular mechanisms and discuss their potential as targets for therapeutic intervention.
Introduction and hypothesis Anterior vaginal wall length (AVL) is on average 6.1±1.3 cm in women with normal support and lengthened in women with cystocele. We hypothesize that AVL is reduced after anterior repair and that women with larger cystoceles will have greater reduction in AVL. Methods Demographic, clinical, and surgical data were collected for women undergoing hysterectomy and anterior repair in whom intraoperative vaginal wall measurements had been made between November 2009 and April 2014. In the operating room, AVL was defined preoperatively as the distance from the hymenal ring to the anterior cervicovaginal junction at the hysterectomy incision site, and postoperatively, from the hymenal ring to the same location on the anterior cuff. During the anterior repair the fibromuscular tissues were plicated using an interrupted technique. Results Measurements were available for 40 women. Average age was 61.7±10 years, median parity was 2.5 and median preoperative Pelvic Organ Prolapse Quantification System (POP-Q) point Ba was 3 cm distal to the hymen. On average, AVL was reduced after surgery by 2.5 cm. Mean postoperative AVL was similar to mean AVL in women with normal pelvic support (6.4±0.8 cm vs 6.1±1.3 cm, p=0.15). Longer preoperative AVLs had greater AVL change (R2=0.78, p= <0.0001). Conclusions In women undergoing anterior repair, mean AVL was reduced by 28 % and returned to the normal range after surgery. These data highlight a rarely discussed effect of anterior repair, which is restoration of normal anterior vaginal wall length.
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