Eleven steroid hormones (SHs: androstene-3,17-dione, estrone, β-estradiol, α-estradiol, testosterone, dehydroepiandrosterone, 17á-hydroxyprogesterone, medroxyprogesterone, megestrol acetate, progesterone, and androsterone) were detected from New Zealand deer (Cervus elaphus var. scoticus) velvet antler (NZA, 鹿茸). A method for the quantification of eleven SHs was established by using ultraperformance liquid chromatography (UPLC)-MS/MS. The linearities (R² > 0.991), limits of quantification (LOQ values, 0.3 ng/mL to 23.1 ng/mL), intraday and interday precisions (relative standard deviation: RSD < 2.43%), and recovery rates (97.3% to 104.6%) for all eleven SHs were determined. In addition, a method for the quantification of three 7-oxycholesterols (7-O-CSs: 7-ketocholesterol, 7α-hydroxycholesterol, and 7β-hydroxycholesterol) in the NZA was established by using an HPLC-photodiode array (PDA) method. The linearities (R² > 0.999), LOQ values (30 ng/mL to 350 ng/mL), intraday and interday precisions (RSD < 1.93%), and recovery rates (97.2% to 103.5%) for the three 7-O-CSs were determined. These quantitative methods are accurate, precise, and reproducible. As a result, it is suggested that the five steroid compounds of androstene-3,17-dione, androsterone, 7-ketocholesterol, 7α-hydroxycholesterol, and 7β-hydroxycholesterol could be marker steroids of NZA. These methods can be applied to quantify or standardize the marker steroids present in NZA.
Androsterone ; Animals ; Antlers ; Chromatography, Liquid ; Deer ; Dehydroepiandrosterone ; Estrone ; Medroxyprogesterone ; Megestrol Acetate ; Methods ; New Zealand ; Progesterone ; Steroids ; Testosterone

BACKGROUND/AIMS: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions that frequently result in fatal outcomes. We investigated cases of SJS and TEN in a regional hospital. METHODS: From 2008 to 2014, SJS and TEN cases were enrolled retrospectively by allergy and dermatology specialists, and their clinical features and severity-of-illness score for TEN (SCORTEN) were assessed. RESULTS: During the 7-year study period, 56 SJS and 14 TEN cases were recruited. The majority (71%) were 40-70 years of age (mean age of male and female patients, 55 and 54 years, respectively). Regarding drugs, anticonvulsants (42.8%) were the most frequently causative, followed by carbonic anhydrase inhibitors (20.0%), antimicrobials (15.7%), allopurinol (7.1%), and non-steroidal anti-inflammatory drugs (7.1%). No fatal case of SJS was seen. However, 7 of the 14 patients with TEN died (50%; mean age, 67 years; 1 of 5 [20%] males and 6 of 9 females [66.7%]). The mortality rate was reflected in the SCORTEN values. Vancomycin, allopurinol, methazolamide (two cases each) and megestrol (one case) were the causative drugs in the seven fatal TEN cases. Treatment modality did not affect the likelihood of death due to TEN. CONCLUSIONS: The causative drugs of, and frequency of mortality due to, SJS and TEN should be recognized by physicians. Elderly females with TEN are at high risk of mortality. SCORTEN values reflect the mortality rate of TEN patients. Early recognition and proper management of SJS and TEN may reduce the mortality rate.
Aged ; Allopurinol ; Anticonvulsants ; Carbonic Anhydrase Inhibitors ; Dermatology ; Drug-Related Side Effects and Adverse Reactions ; Fatal Outcome ; Female ; Humans ; Hypersensitivity ; Male ; Megestrol ; Methazolamide ; Mortality ; Retrospective Studies ; Specialization ; Stevens-Johnson Syndrome* ; Vancomycin

OBJECTIVE: To report our 15-year institutional experience of fertility-sparing treatment in young patients with early endometrial cancer (EC) treated by combined hysteroscopic resection and progestin therapy. METHODS: Twenty-eight patients (stage IA, G1 and 2 endometrioid EC) wishing to preserve their fertility were enrolled into this prospective study. Hysteroscopic resection was used to resect the tumor, endometrium adjacent to the tumor and myometrium underlying the tumor. Adjuvant hormonal therapy consisted of oral megestrol acetate or levonorgestrel intrauterine device for 6 months or more. RESULTS: After 3 months from the progestin start date, 25 patients (89.3%) showed a complete regression (median time to complete regression, 3 months [range, 3-9 months]), two (7.1%) showed persistent disease, while one patient (3.6%) presented with progressive disease and underwent definitive surgery (stage IA, G3 endometrioid). At 6 months, one of the two patients with persistent disease underwent definitive surgery (stage IA, G1 endometrioid), while the other one was successfully re-treated. Two recurrences were observed (7.7%) both involving the endometrium and synchronous ovarian cancer. The median duration of complete response was 94.5 months (range, 8-175 months). More than half of the responders (57.7%) attempted to conceive with 93.3% and 86.6% pregnancy and live birth rates, respectively. CONCLUSION: The addition of a standardized three-step resectoscopy to progestin would seem to improve the efficacy of progestin alone. High pregnancy and live birth rates were observed in women attempting to conceive.
Animals ; Endometrial Neoplasms* ; Endometrium ; Female ; Fertility Preservation ; Fertility* ; Humans ; Hysteroscopy ; Intrauterine Devices ; Levonorgestrel ; Live Birth ; Megestrol Acetate ; Mice ; Myometrium ; Ovarian Neoplasms ; Pregnancy ; Prospective Studies ; Recurrence

Anorexia is one of the most common issues in older patients. Although there is a tendency for loss of appetite in older persons due to decreased physical activity and reduced resting metabolic rate, this physiological anorexia of aging can easily develop into progressive anorexia and weight loss. This pathologic anorexia and resultant weight loss is associated with increased morbidity and mortality, especially in the frail elderly. To prevent older persons from entering a vicious cycle of frailty, that is, anorexia-malnutrition-sarcopenia-functional impairment, routine screening for anorexia and malnutrition should be implemented in geriatric clinical practice. All anorexic elderly patients should be strongly encouraged to maintain their nutrition, and appetite stimulants can be considered if non-pharmacological interventions are not effective. Although there are no US or Korea Food and Drug Administration approved medications for geriatric-specific anorexia and weight loss, several appetite stimulants can be prescribed and are used widely. Megestrol acetate is the most widely studied and commonly used of these drugs. Cyproheptadine, dronabinol, mirtazapine, corticosteroids, anabolic steroids (e.g., testosterone or oxandrolone), and growth hormone are also effective in increasing appetite or weight. However, the use of these orexigenic agents should occur only after their benefit-to-risk ratio has been carefully considered.
Adrenal Cortex Hormones ; Aged ; Aging ; Anorexia ; Appetite Stimulants* ; Appetite* ; Cyproheptadine ; Diethylpropion ; Dronabinol ; Frail Elderly ; Growth Hormone ; Humans ; Korea ; Malnutrition ; Mass Screening ; Megestrol Acetate ; Mortality ; Motor Activity ; Steroids ; Testosterone ; United States Food and Drug Administration ; Weight Loss

In generic drug development, comparative pharmacokinetic (PK) studies are conducted to assess equivalence in pharmacokinetics and safety profiles between test and reference formulations. However, there is no established quantitative approach available for safety assessment. This study aimed to propose a method for drug safety evaluation in generic drug development, as assessed by drug influence on blood pressure and heart rate change. Data were taken from a randomized, open label, 2-way cross-over comparative PK study for megestrol conducted in 39 healthy male volunteers. Vital signs of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were measured at 0 (pre-dose), 4, 8, 12, 24, 48, 72, 96 and 120 hours after the dose. Safety parameters used in the analysis were area under vital sign change versus time curve to the last measured time (AUVlast) and maximum vital sign change (Vmax). Considering highly variable nature of vital signs, the scaled bioequivalence approach developed by US FDA was adopted as a decision rule for safety evaluation between formulations. With the FDA scaled approach, 90% confidence intervals of geometric mean ratio for DBP, 0.7969~1.0377 for Vmax and 0.7304~1.0660 for AUVlast, were both included in the equivalence ranges of 0.7694~1.2997 and 0.6815~1.4674, respectively, and similarly, those for HR were included in their respective scaled equivalence limits, while SBP satisfied the conventional equivalence criterion of 0.8-1.25. These results illustrate the feasibility of applying the suggested approach in cardiovascular safety evaluation in a generic drug.
Blood Pressure ; Heart Rate ; Humans ; Male ; Megestrol ; Pharmacokinetics ; Therapeutic Equivalency ; Vital Signs ; Volunteers

No abstract available.
Antineoplastic Agents, Hormonal/*therapeutic use ; Endometrial Hyperplasia/*drug therapy ; Female ; Humans ; Hypoglycemic Agents/*therapeutic use ; Megestrol Acetate/*therapeutic use ; Metformin/*therapeutic use

OBJECTIVE: To compare the efficacy of metformin plus megestrol acetate (MA) with that of MA alone for treating endometrial atypical hyperplasia (EAH). METHODS: This pilot study included 16 EAH patients who met at least one metabolic syndrome (MS) criterion and received either adjunctive metformin plus MA (MET group) or MA monotherapy (MA group). Each patient in the MA group received 160 mg of MA daily, whereas patients in the MET group received the same dose of MA plus 0.5 g of metformin thrice daily. Treatment response was assessed by histological examination of dilation and curettage specimens obtained after 12 weeks of therapy. RESULTS: Each group had eight patients, and half of the patients in each group were diagnosed with MS. The complete response (CR) rate was 75% (6/8) in the MET group and 25% (2/8) in the MA group (p=0.105). Complications of MS did not affect the response rates in either group. In the MET group, 75% (3/4) of the patients had CR in the presence or absence of MS. In the MA group, 50% (2/4) of the patients with MS had CR, whereas no patient without MS had CR. No irreversible toxicities were observed. CONCLUSION: Metformin plus MA may be a potential alternative therapy for treating EAH, and the MS status of patients may have no effect on the efficacy of metformin plus MA therapy.
Adult ; Antineoplastic Agents, Hormonal/*therapeutic use ; Drug Therapy, Combination ; Endometrial Hyperplasia/complications/*drug therapy/metabolism ; Female ; Humans ; Hypoglycemic Agents/*therapeutic use ; Megestrol Acetate/*therapeutic use ; Metabolic Syndrome X/complications/metabolism ; Metformin/*therapeutic use ; Pilot Projects ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Single-Blind Method ; Treatment Outcome

A rapid and highly selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of megestrol in human plasma was described using medrysone as internal standard (IS). Blood samples were collected from 20 healthy volunteers after oral administration of 160 mg megestrol acetate dispersible tablets. The analytes were extracted by liquid-liquid extraction procedure and separated on a hanbon lichrospher column with the mobile phase of methanol and water containing 0.1% formic acid and 20 mmol/L ammonium acetate (5:1, v/v). Positive ion electrospray ionization with multiple reaction-monitoring mode (MRM) was employed by monitoring the transitions m/z 385.5-325.4 and m/z 387.5-327.4 for megestrol and medrysone, respectively. Under the isocratic separation conditions, the chromatographic run time was approximately 2.54 min for megestrol and 2.59 min for medrysone. The calibration curve range was from 0.5 to 200.0 ng/mL. The inter-batch and intra-batch precision and accuracy were less than 5.2% relative standard deviation (RSD) and 6.4% relative error (RE). The proposed method was successfully applied in the bioequivalence study of megestrol acetate dispersible tablets.
Calibration ; Gas Chromatography-Mass Spectrometry ; methods ; standards ; Humans ; Megestrol ; blood ; chemistry ; pharmacokinetics ; Therapeutic Equivalency

There are concerns whether megestrol acetate (MA) stimulates the growth of prostate cancer in castration-resistant prostate cancer (CRPC). We evaluated the effect of cumulative doses of MA on the disease-specific survival (DSS) in patients with CRPC who were receiving Docetaxel-based chemotherapy. From July 2003 through June 2009, we identified 109 consecutive patients with CRPC and who had received docetaxel-based chemotherapy. Of these patients, 68 (62.4%) have not received MA, whereas 21 patients (19.3%) and 20 patients (18.3%) had received low dose MA (total < or = 18,400 mg) and high dose MA (total > 18,400 mg), respectively. We assessed the effect of several variables on DSS. None of the clinicopathological variables differed among the three groups. When comparing DSS using Kaplan-Meier analysis, there was no statistically significant survival differences among the three groups (P = 0.546). Using multivariate Cox proportional analyses with backward elimination, the number of docetaxel cycles was only significant factor predicting DSS (HR: 0.578, 95% CI: 0.318-0.923, P = 0.016). Cumulative doses of MA as adjuvant treatment for patients with CRPC and who are receiving docetaxel-based chemotherapy, did not affect their DSS. Therefore, MA can be safely administered in cachexic patients with CRPC.
Aged ; Aged, 80 and over ; Anorexia/complications/*drug therapy ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents, Hormonal/*therapeutic use ; Cachexia/complications/*drug therapy ; Castration ; Humans ; Kaplan-Meier Estimate ; Male ; Megestrol Acetate/*therapeutic use ; Middle Aged ; Proportional Hazards Models ; Prostatic Neoplasms/complications/*drug therapy/mortality ; Taxoids/therapeutic use

PURPOSE: The purpose of this study is to evaluate the prescription of essential or futile medications for terminal cancer patients during their final admission. MATERIALS AND METHODS: We conducted a retrospective review of the medical charts of terminally ill cancer patients admitted to the Hemato-oncology Department of two teaching hospitals from March 1, 2007 to December 31, 2009. Essential medications were based on the drugs listed by the International Association for Hospice and Palliative Care, while futile medications were defined when short-term benefit to patients with respect to survival, quality of life, or symptom control was not anticipated. RESULTS: A total of 196 patients were included. Among essential medications, strong opioids were the most frequently prescribed drugs during the last admission (62.2% fentanyl, 44.3% morphine), followed by megestrol (46.0%), and metoclopramide (37.2%); 51% of gastric protectors were prescribed with potential futility. Anti-hypertensive and antiglycemic agents were administered to those who experienced arterial blood pressure below 90 mm Hg (47.3%) or presented with a single measurement of fasting glucose below 50 mg/dL (10.7%), respectively. Statins were prescribed to 6.1% (12/196) of patients, and 75% of those prescriptions were regarded as futile. CONCLUSION: Our data suggest that effective prescription of essential medications and withdrawal from futile medications should be actively reconciled for improvement of a patient's end-of-life care.
Analgesics, Opioid ; Arterial Pressure ; Fasting ; Fentanyl ; Glucose ; Hospices ; Hospitals, Teaching ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Medical Futility ; Megestrol ; Metoclopramide ; Palliative Care ; Prescriptions ; Quality of Life ; Retrospective Studies ; Terminally Ill