Daily Endocrinology Research Analysis

OBJECTIVE: Asherman syndrome (AS) is characterized by intrauterine adhesions/fibrosis, resulting from damage to the endometrial basalis layer. The consequences of AS include infertility, recurrent pregnancy loss, preterm rupture of membranes, and placental abruption. Hysteroscopic adhesiolysis does not consistently restore endometrial function; there is a need for more effective treatments. Bone marrow-derived mesenchymal stem cells (BMD-MSCs) circulate systemically and contribute to tissue repair/regeneration, suggesting that they may serve as a source of progenitor cells for endometrial regeneration. Increasing the supply of BMD-MSCs to the endometrium may treat AS by allowing for regeneration/replenishment of endometrial progenitor cells. Mobilization of autologous BMD-MSCs using AMD3100, a CXC-motif-receptor-4 antagonist, is approved for bone marrow transplantation. We aimed to determine whether the optimal timing of AMD3100 administration-on the basis of CXCL12 production-would better recruit BMD-MSCs in a murine model of severe AS and restore functioning endometrium/fertility. DESIGN: Severe AS murine model. SUBJECTS: C57BL/6 mice in the diestrus phase undergoing surgical AS induction. EXPOSURE: Single injection with AMD3100 (treatment) or vehicle (saline). AMD3100 administration timing was based on the determination of maximum CXCL12 release after AS induction. Mice were then mated. MAIN OUTCOME MEASURES: Time to pregnancy, litter size, and miscarriage rate. RESULTS: Maximum uterine CXCL12 production occurred 48 hours after AS induction; thus, AMD3100 vs. saline was administered 48 hours after induction. Of the AMD3100-treated mice, all achieved pregnancy and delivered. The treatment group became pregnant and delivered significantly sooner, indicating a faster time to conception (20 vs. 26 days). The treatment group had significantly larger litter sizes (6.5 vs. 4.2 pups) and significantly more live pups at delivery than the control group (6.0 vs. 2.7). CONCLUSION: AMD3100 had a significant effect on uterine repair and regeneration in AS. The likelihood of pregnancy was significantly higher and more rapid in AS mice treated with AMD3100. Treated mice also had larger litter sizes and fewer miscarriages than controls. Furthermore, we determined for the first time the levels of CXCL12 in uteri after uterine injury, which allowed for the determination of the optimal timing of AMD3100 administration, to ensure mobilized BMD-MSCs homed to the uterus.

BACKGROUND: Isotretinoin is the first-line treatment for severe acne, but its effects on adolescent growth remain unclear. OBJECTIVE: To assess the effects of isotretinoin on final adult height and height velocity in adolescents treated for acne. METHODS: This retrospective cohort study used the Rochester Epidemiology Project to identify patients diagnosed with acne between 2005 and 2021 who initiated isotretinoin or oral antibiotics before age 15. Height velocity was calculated using measurements taken within 1 year pre- and postmedication initiation, and final height was recorded at 18 years. Multivariable regression models adjusted for age and sex. RESULTS: Among 226 patients treated with isotretinoin and 1179 controls, final height did not differ significantly between groups (-0.67 cm; CI: -2.21 to 0.87). However, patients treated with isotretinoin had a lower postmedication initiation height velocity (-0.12 cm/month; CI: -0.21 to -0.04, P = .005) and a greater reduction in post- versus premedication initiation height velocity (-0.31 cm/month; CI: -0.54 to -0.07, P = .011). No significant dosage effects were observed. LIMITATIONS: The study was limited by sample size, potential unmeasured confounders, and a predominantly non-Hispanic white population. CONCLUSIONS: While isotretinoin may reduce height velocity, it is not associated with negative effects on final adult height among adolescents treated for acne.

BACKGROUND: For preventing Vitamin D (VD) insufficiency, several VD supplementation guidelines were established worldwide. In Japan, no nationwide guidelines for preventing VD insufficiency have been implemented, whereas guidelines for preventing vitamin K (VK) deficiency-related bleeding recommend weekly supplementation of VK. The aim of this study is to clarify whether weekly VD plus VK supplementation during the early neonatal period prevents VD insufficiency at one month of age. METHODS: We retrospectively analyzed serum 25-hydroxyvitamin D (25(OH)D) levels of 555 one-month-old infants born between 2017 and 2023. Infants were classified into the control group (not supplemented), weekly group (1000 IU/week), and daily group (240 IU/day). We compared serum 25(OH)D levels among the three groups. Multivariable logistic regression analyses adjusted for formula intake and BMI were performed to better estimate the effect of VD supplementation on the prevention of VD insufficiency. RESULTS: We included 414, 55, and 86 infants in the control, weekly, and daily groups, respectively. All infants received weekly supplementation of VK. Serum 25(OH)D levels in the weekly and daily groups were higher than those in the control group (median (ng/mL): control 9.7 vs weekly 22.2, P < 0.001; control vs daily 23.0, P < 0.001). The frequencies of VD insufficiency were 370/414 (89.4 %), 11/55 (20.0 %), and 22/86 (25.6 %) in the control, weekly, and daily groups, respectively. Adjusted odds ratios of VD insufficiency compared to the control were 0.038 (95 % confidence intervals (95 %CI): 0.017, 0.085) and 0.036 (95 %CI: 0.019, 0.067) in the weekly and daily groups, respectively. No infant with VD excess was observed. CONCLUSION: Our results demonstrated that combined weekly supplementation of VD and VK during early infancy can prevent VD insufficiency at one month of age without causing VD excess. This finding may provide evidence for the development of nationwide prophylaxis for VD insufficiency in regions lacking specific guidelines.