Objectives: The current study aimed at determining the effects of degarelix on bone turnover, bone densitometry, and bone mechanical strength in male rats.
Methods: Eighteen male Sprague-Dawley rats were randomly divided into sham (SHAM), orchidectomized (ORX), and degarelix-induced (DGX) groups. Chemical castration was performed by subcutaneous degarelix injection (2 mg/kg) at the scapular region. The rats were scanned for baseline bone mineral area (BMA), bone mineral content (BMC), and bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA). Following six weeks of experimental period, BMA, BMC, and BMD were measured again with DXA and blood was collected for testosterone and bone biomarkers (osteocalcin and C-terminal of type I collagen crosslink (CTX-1)) measurements. The rats were euthanized and femora were dissected for bone biomechanical strength analysis.
Results: Bilateral orchidectomy and degarelix administration significantly lowered serum testosterone level, decreased whole body BMC, femoral BMA, femoral BMC, and femoral BMD (P < 0.05) compared with the SHAM group. However, no significant changes were observed in bone biochemical markers and bone mechanical strength in all experimental groups.
Conclusions: In conclusion, degarelix administration had comparable effects on bone as bilateral orchidectomy. Administration of degarelix provides an alternative method of inducing testosterone deficient-osteopenia in male rats without need for removing the testes.
Case Presentation: A 50-year-old lady developed recurrent Cushing's disease after being in remission following transsphenoidal surgery (TSS) for a left pituitary microadenoma 16 years ago. The repeat MRI showed a right pituitary microadenoma (1.7 mm × 1.3 mm) for which she underwent a second TSS. However, she continued to have persistent hypercortisolism despite repeated MRIs showing absence of tumour recurrence. She refused bilateral adrenalectomy and external radiotherapy. Ketoconazole was commenced at 200 mg twice daily for disease control but this was hindered by intolerable side effects including pruritus and skin exfoliation. In the meantime, she suffered a right hypertensive basal ganglia hemorrhage. Treatment was subsequently switched to cabergoline and the dose titrated to 0.5 mg daily. Fluconazole 400 mg daily was later added to control the persistent disease. Her clinical and biochemical parameters improved markedly three months after the addition of fluconazole. No adverse event was reported. Her disease has remained stable for the last 15 months up until the time of the recent clinic review.
Conclusions: This case demonstrates the long-term efficacy of fluconazole in tandem with cabergoline for the control of recurrent Cushing's disease.
EVIDENCE ACQUISITION: PubMed searches were conducted using the keywords 'statin, effect, and lipid profile' from database inception through March 2016. In this review, 718 articles were retrieved from the primary search. After reviewing the titles, abstracts, and full texts, we found that 59 studies met our inclusion criteria. These also included subsequent reference searches of retrieved articles.
RESULTS: CURVES study compared the effect on lipid profile between atorvastatin and other statins. This study demonstrated that low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) were reduced more with atorvastatin compared to simvastatin, pravastatin, lovastatin, and fluvastatin. However, simvastatin provided a greater elevation of high-density lipoprotein cholesterol (HDL-C) compared to atorvastatin. The STELLAR trial was based on dose-to-dose comparisons between atorvastatin and rosuvastatin efficacy in reducing LDL-C. Te present study also revealed that as the doses of rosuvastatin, simvastatin, and pravastatin increased, HDL-C also increased, with rosuvastatin having the greatest effect. However, HDL-C levels decreased as the dose of atorvastatin increased. The DISCOVERY study involving the Asian population revealed that the percentage of patients achieving the European goals for LDL-C and TC at 12 weeks was higher in rosuvastatin group compared to atorvastatin group.
CONCLUSIONS: The effects of statins on lipid profile are dose dependent. Most studies showed that rosuvastatin has the best effect on lipid profile. Prescribing lower doses of statins in Asians seems necessary.
METHODS: Three-month-old Sprague-Dawley male rats (n = 18) were randomized equally into 3 groups. Bilateral orchidectomy was performed on 2 groups. The sham group was subjected to similar surgical stress, but their testes were retained. One of the orchidectomized groups received intramuscular injection of 7 mg/kg testosterone enanthate suspended in peanut oil weekly and the other 2 groups received equivolume of peanut oil injection. After 8 weeks, the rats were sacrificed and their blood was collected for the analysis of the levels of inflammatory cytokines and testosterone.
RESULTS: Testosterone level was significantly lower in the untreated orchidectomized group compared to the sham group. Testosterone replacement significantly increased the level of testosterone in the orchidectomized rats compared to the sham and untreated orchidectomized rats. Interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNFα) showed an increasing trend in orchidectomized rats, albeit not statistically significant. Interleukin-6 (IL-6) level increased significantly in the orchidectomized group compared to the sham group. Testosterone replacement at the supraphysiological dose did not alter the level of inflammatory cytokines significantly in orchidectomized rats.
CONCLUSIONS: Testosterone deficiency can elicit a state of low-grade inflammation, shown by an increase in interleukin-6 level, but exogenous supraphysiological testosterone replacement does not suppress the inflammation.