Effects of high fat diet on metabolic health vary by age of menopause onset.

Menopause accelerates metabolic dysfunction, including (pre-)diabetes, obesity and visceral adiposity. However, the effects of endocrine vs. chronological aging in this progression are poorly understood. We hypothesized that menopause, especially in the context of middle-age, would exacerbate the metabolic effects of a high fat diet. Using young-adult and middle-aged C57BL/6J female mice, we modeled diet-induced obesity via chronic administration of high fat (HF) diet vs. control diet. We modeled peri-menopause/menopause via injections of 4-vinylcyclohexene diepoxide, which accelerates ovarian failure vs. vehicle. We performed glucose tolerance tests 2.5 and 7 months after diet onset, during the peri-menopausal and menopausal phases, respectively. Peri-menopause increased the severity of glucose intolerance and weight gain in middle-aged, HF-fed mice. Menopause increased weight gain in all mice regardless of age and diet, while chronological aging drove changes in adipose tissue distribution towards more visceral vs. subcutaneous adiposity. These data are in line with clinical data showing that post-menopausal women are more susceptible to metabolic dysfunction and suggest that greater chronological age exacerbates the effects of endocrine aging (menopause). This work highlights the importance of considering both chronological and endocrine aging in studies of metabolic health.

Treatment with brain specific estrogen prodrug ameliorates cognitive effects of surgical menopause in mice.

Menopause is an endocrine shift leading to increased vulnerability for cognitive impairment and dementia risk factors, in part due to loss of neuroprotective circulating estrogens. Systemic replacement of estrogen post-menopause has limitations, including risk for estrogen-sensitive cancers. A promising therapeutic approach therefore might be to deliver estrogen only to the brain. We examined whether we could enhance cognitive performance by delivering estrogen exclusively to the brain in ovariectomized mice (a surgical menopause model). We treated mice with the prodrug 10ß,17ß-dihydroxyestra-1,4-dien-3-one (DHED), which can be administered systemically but is converted to 17ß-estradiol only in the brain. Young and middle-aged C57BL/6 J mice received ovariectomy and subcutaneous implant containing vehicle or DHED and underwent cognitive testing to assess memory after 1-3.5 months of treatment. Low and medium doses of DHED did not alter metabolic status in middle-aged mice. In both age groups, DHED treatment improved spatial memory in ovariectomized mice. Additional testing in middle-aged mice showed that DHED treatment improved working and recognition memory in ovariectomized mice. These results lay the foundation for future studies determining if this intervention is as efficacious in models of dementia with comorbid risk factors.

Current Trends in the Use of Buccal Grafts During Urethroplasty Among Society of Genitourinary Reconstructive Surgeons.

OBJECTIVE: To analyze current standards in urethroplasty by urologists employing buccal mucosal grafts (BMG) for treating urethral stricture disease (USD). METHODS: An IRB-approved online survey was distributed to members of the Society of Genitourinary Reconstructive Surgeons (GURS) between July and October 2022 to assess BMG utilization in urethroplasty. Questions covered surgeon experience, graft harvest site, graft length, surgical technique, and perceived success rates. RESULTS: Of 350 invited GURS members, 134 responded (38%). Sixty-nine percentage were GURS fellowship-trained, performing 10-30 urethroplasties annually. Ninety-five percentage harvested their own grafts, with 99% preferring buccal mucosa as the primary site. Buccal mucosa was favored over fasciocutaneous flap for penile urethroplasty, regardless of circumcision status (95% with, 84% without). For bulbar urethroplasty with BMG, dorsal graft placement was favored (66%) over ventral (34%). Most surgeons (90%) preferred multiple BMGs over combined graft/flap for panurethral strictures. When harvesting long grafts, 56% preferred using both cheeks. Anastomotic urethroplasty was preferred over buccal graft urethroplasty for short bulbomembranous stenosis post-radiotherapy (63% vs 37%). Surgeons reported a success rate of 80%-90% (53%). CONCLUSION: The expanded scope of reconstructive urology has led to increased use of BMG in diverse urethral reconstructions. Buccal grafts are now preferred for penile, bulbar, and panurethral strictures, demonstrating high perceived success rates in the reconstructive community.

Effects of High Fat Diet on Metabolic Health Vary by Age of Menopause Onset.

Menopause accelerates metabolic dysfunction, including (pre-)diabetes, obesity and visceral adiposity. However, the effects of endocrine vs. chronological aging in this progression are poorly understood. We hypothesize that menopause, especially in the context of middle-age, will exacerbate the metabolic effects of a high fat diet. Using young-adult and middle-aged C57BL/6J female mice, we modeled diet-induce obesity via chronic administration of high fat (HF) diet vs. control diet. We modeled peri-menopause/menopause via injections of 4-vinylcyclohexene diepoxide, which accelerates ovarian failure vs. vehicle. We performed glucose tolerance tests 2.5 and 7 months after diet onset, during the peri-menopausal and menopausal phases, respectively. Peri-menopause increased the severity of glucose intolerance and weight gain in middle-aged, HF-fed mice. Menopause increased weight gain in all mice regardless of age and diet, while chronological aging drove changes in adipose tissue distribution towards more visceral vs. subcutaneous adiposity. These data are in line with clinical data showing that post-menopausal women are more susceptible to metabolic dysfunction and suggest that greater chorological age exacerbates the effects of endocrine aging (menopause). This work highlights the importance of considering both chronological and endocrine aging in studies of metabolic health.