Circulating and intraprostatic sex steroid hormonal profiles in relation to male pattern baldness and chest hair density among men diagnosed with localized prostate cancers

Background: Prospective cohort studies of circulating sex steroid hormones and prostate cancer risk have not provided a consistent association, despite evidence from animal and clinical studies. However, studies using male pattern baldness as a proxy of early-life or cumulative androgen exposure have reported significant associations with aggressive and fatal prostate cancer risk. Given that androgens underlie the development of patterned hair loss and chest hair, we assessed whether these two dermatological characteristics were associated with circulating and intraprostatic concentrations of sex steroid hormones among men diagnosed with localized prostate cancer. Methods:We included 248 prostate cancer patients from the NCI Prostate Tissue Study, who answered surveys and provided a pre-treatment blood sample as well as fresh frozen adjacent normal prostate tissue. Male pattern baldness and chest hair density were assessed by trained nurses before surgery. General linear models estimated geometric means and 95% confidence intervals (95%CIs) of each hormone variable by dermatological phenotype with adjustment for potential confounding variables. Subgroup analyses were performed by Gleason score (\u3c7 vs ≥7) and race (European American vs. African American). Results: We found strong positive associations of balding status with serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone-binding globulin (SHBG), and a weak association with elevated intraprostatic testosterone. Conversely, neither circulating nor intraprostatic sex hormones were statistically significantly associated with chest hair density. Age-adjusted correlation between binary balding status and three-level chest hair density was weak (r = 0.05). There was little evidence to suggest that Gleason score or race modified these associations. Conclusions: This study provides evidence that balding status assessed at a mean age of 60 years may serve as a clinical marker for circulating sex hormone concentrations. The weak-to-null associations between balding status and intraprostatic sex hormones reaffirm differences in organ-specific sex hormone metabolism, implying that other sex steroid hormone-related factors (eg, androgen receptor) play important roles in organ-specific androgenic actions, and that other overlapping pathways may be involved in associations between the two complex conditions

Association of Apremilast With Vascular Inflammation and Cardiometabolic Function in Patients With Psoriasis: The VIP-A Phase 4, Open-label, Nonrandomized Clinical Trial

IMPORTANCE: Psoriasis is an inflammatory condition associated with metabolic and cardiovascular disease. Apremilast, a phosphodiesterase 4 inhibitor, is commonly used for psoriasis and can cause weight loss. OBJECTIVE: To determine the association between apremilast and aortic vascular inflammation as assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), cardiometabolic markers (primary outcomes at week 16), and abdominal fat composition. DESIGN, SETTING, AND PARTICIPANTS: A single-arm, open-label, interventional, nonrandomized clinical trial in which the imaging and laboratory outcomes were measured by an investigator who was blinded to time was conducted between April 11, 2017, and August 17, 2021, at 7 dermatology sites in the United States. A total of 101 patients with moderate to severe psoriasis were screened, 70 enrolled, 60 completed week 16, and 39 completed week 52. INTERVENTION: Apremilast, 30 mg, twice daily. MAIN OUTCOMES AND MEASURES: Aortic vascular inflammation (measured by FDG-PET/CT), 68 cardiometabolic biomarkers, and abdominal fat composition (measured by CT) at week 16 and week 52 compared with baseline. RESULTS: The mean (SD) age of the 70 patients was 47.5 (14.6) years, 54 were male (77.1%), 4 were Black (5.7%), and 58 were White (82.9%). There was no change in aortic vascular inflammation at week 16 (target to background ratio, -0.02; 95% CI, -0.08 to 0.05; P = .61) or week 52 (target to background ratio, -0.07; 95% CI, -0.15 to 0.01; P = .09) compared with baseline. At week 16, potentially beneficial decreases in interleukin 1b, valine, leucine, isoleucine, fetuin A, and branched-chain amino acids were observed. At week 52 compared with baseline, potentially beneficial decreases in ferritin, β-hydroxybutyrate, acetone, and ketone bodies, with an increase in apolipoprotein A-1, were observed, but there was a reduction in cholesterol efflux. There was an approximately 5% to 6% reduction in subcutaneous and visceral adiposity at week 16 that was maintained at week 52. CONCLUSIONS AND RELEVANCE: The findings of this nonrandomized clinical trial suggest that apremilast has a neutral association with aortic vascular inflammation, variable but generally beneficial associations with a subset of cardiometabolic biomarkers, and associations with reductions in visceral and subcutaneous fat, indicating that the drug may have an overall benefit for patients with cardiometabolic disease and psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03082729

Photodynamic destruction of endometrial tissue with topical 5-aminolevulinic acid in rats and rabbits

ObjectiveThe goal of this study was to determine the optimal parameters for photodynamic endometrial destruction with topically applied 5-aminolevulinic acid, a precursor for the endogenous synthesis of the fluorescent photosensitizer protoporphyrin IX.Study design5-Aminolevulinic acid pharmacokinetics were measured in rat and rabbit models by analyzing tissue frozen sections 3 to 12 hours after topical administration. Dose-response studies were conducted for 100 to 400 mg/ml 5-aminolevulinic acid. Photodynamic therapy was performed intraluminally, and tissue morphologic features were evaluated 3 and 7 days after treatment.ResultsPeak fluorescence was observed 3 hours after topical administration. Glandular fluorescence significantly exceeded stromal and myometrial in all studies, particularly for 200 mg/ml 5-aminolevulinic acid. Histologic studies revealed persistent epithelial destruction with minimal regeneration.ConclusionTopical 5-aminolevulinic acid photodynamic therapy can be used for highly effective, long-lasting destruction of endometrial epithelium. However, optical dosimetry can vary, particularly in the rabbit model, and this appears to have an impact on long-term reepithelialization

PHOTODYNAMIC THERAPY OF THE CANINE PERITONEUM - NORMAL TISSUE-RESPONSE TO INTRAPERITONEAL AND INTRAVENOUS PHOTOFRIN FOLLOWED BY 630NM LIGHT

A toxicity study was performed in a canine model to explore the feasibility of using intraperitoneal photodynamic therapy for patients with peritoneal carcinomatosis. Dogs received 1.25 mg/kg Photofrin II both intravenously (48 hours) and intraperitoneally (2 hours) before intraperitoneal light treatment. The entire peritoneal surface was illuminated with 0.57-0.74 J/cm2 of red light (630 nm). Thirteen dogs were treated: 4 control and 9 full treatment. Of the fully treated dogs, 5 received a single treatment and 4 received 3 treatments. The dogs were evaluated clinically and pathologically for immediate (4 days) and late (60 days) side effects. All animals tolerated the treatment without significant morbidity. Postoperative blood tests were normal except for low lymphocyte counts and elevated liver transaminases, both of which normalized rapidly. Histopathologically, there was approximately a 50% incidence of mild inflammatory peritoneal response. This study provides the basis for a Phase I human trial