To investigate the effects of the property of drugs and the structure of drug delivery devices on the drug release rate, the effects of sealing methods, length, thickness and drug-loading manner of the silicone tubes on the drug release rate were examined using progestin, testosterone, estradiol as the delivery drugs. The results showed that the property of the drug was the crucial factor to the drug release rate. The sealing methods, length, thickness and drug status of the silicone tubes had significant effects on the drug release rate and the effects were closely related to the property of the drugs. In addition, our newly developed glass-silicone tube has larger drug deposition capability and smaller drug release area, offers an effective and convenient method for the sustained drug delivery with quick release traits in vivo.
Delayed-Action Preparations ; chemistry ; Drug Carriers ; administration & dosage ; chemistry ; Drug Delivery Systems ; Estradiol ; administration & dosage ; Progesterone Congeners ; administration & dosage ; Silicones ; Testosterone ; administration & dosage

Estrogen deficiency is the one of pathogenetic causes of postmenopausal osteoporosis. Exogenous estrogen may prevent postmenopausal bone loss, so to prevent postmenopausal osteoporosis and osteoporotic fracture. The effect of estrogen on postmenopausal syndrome can not be substituted with other medicine. However, the attention should be paid to the safety of hormone replacement therapy (HRT) during its long term use, and HRT should be used individually.
Aged ; Drug Therapy, Combination ; Estrogen Replacement Therapy ; Estrogens, Conjugated (USP) ; administration & dosage ; Female ; Humans ; Medroxyprogesterone ; administration & dosage ; Middle Aged ; Osteoporosis, Postmenopausal ; prevention & control ; Progesterone Congeners ; administration & dosage

Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.
Antineoplastic Agents, Hormonal/adverse effects ; Disease Management ; Disease Progression ; Endometrial Hyperplasia/classification/etiology/*therapy ; Female ; Gonadotropin-Releasing Hormone/therapeutic use ; Humans ; Hysterectomy ; Molecular Targeted Therapy/methods ; Progesterone Congeners/therapeutic use ; Risk Factors ; Tamoxifen/adverse effects

Adult ; Body Mass Index ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Follicle Stimulating Hormone ; blood ; Humans ; Luteinizing Hormone ; blood ; Phytotherapy ; Polycystic Ovary Syndrome ; blood ; drug therapy ; Progesterone Congeners ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVETo study the reversal effect of nomegestrol acetate (NOM) on mutidrug resistance (MDR) in MCF7/ADR and its mechanism.

METHODSUsing tetrazolium dye assay, effects of various concentrations of NOM on sensitivity to ADR in MCF7/ADR was studied. Expression of MDR related genes MDR1, glutathoine S-transferase Pi (GSTpi), Topoisomerase II alpha (Topo II alpha) and MDR related protein (MRP) were assayed by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry assay. Using flow cytometry (FCM), intracellular ADR concentration effects on cell cycle were observed.

RESULTSNOM significantly reversed MDR in MCF7/ADR. After NOM 20, 10 and 5 micromol/L treatment, the chemosensitivity to ADR increased to 21, 12 and 8 times. The reversal activity of NOM was stronger than that of the precursor compound megestrol acetate, and was comparable to that of verapamail. After treatment with NOM 5 micromol/L both MDR1 and GSTpi mRNA genes expression began to decline on D2 (P < 0.05, & P < 0.01) and reached the lowest level on D3 (both P < 0.01), but the expression levels began to rise on D6 again (both P < 0.05). The expression of MRP and Topo II alpha gave no significant change. Changes of P-gp and GSTpi protein expressions were similar to those of their mRNA expressions, showing early decline and late rise. Two hours after NOM 20, 10, and 5 micromol/L treatment, intracellular ADR concentration increased 2.7, 2.3 and 1.5 times, respectively. FCM data showed that after forty-eight hours, combined administration of NOM (20 micromol/L) and ADR (from low concentration to high concentration), MCF7/ADR cells showed gradual arrest in the G(2)M phase with the increase of ADR dose.

CONCLUSIONNOM has strong reversal effects on MDR in MCF7/ADR. The reversal takes place via different routes, i.e. down regulating mRNA and protein expression levels of MDR1 and GSTpi, increasing intracellular drug concentration, and enhancing the arrest of ADR in cells at G(2)M phase.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Antigens, Neoplasm ; Breast Neoplasms ; genetics ; pathology ; Cell Survival ; drug effects ; DNA Topoisomerases, Type II ; genetics ; metabolism ; DNA-Binding Proteins ; Drug Resistance, Neoplasm ; genetics ; Gene Expression Regulation, Neoplastic ; drug effects ; Glutathione S-Transferase pi ; Glutathione Transferase ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Inhibitory Concentration 50 ; Isoenzymes ; genetics ; metabolism ; Megestrol ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; Norpregnadienes ; pharmacology ; Progesterone Congeners ; pharmacology ; RNA, Messenger ; drug effects ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured ; Verapamil ; pharmacology

Preterm birth (PTB) is defined as birth before 37 completed weeks of gestation, which occurs in approximately 10% of all pregnancies. Prior PTB history and short cervical length (CL) are the most significant predictors of PTB. Prior PTB history can increase the risk of recurrence of PTB more than two-fold in the next pregnancy. A short CL of less than 25 mm as measured by ultrasound between 16 and 24 weeks of gestation has been shown to be the most reliable predictor of an increased risk of PTB. Progesterone is one of the few proven effective methods of preventing PTB in women with a previous history of spontaneous PTB and women with a short CL. Progestins are available in natural micronized or synthetic formulations for intramuscular or vaginal (tablet or gel) administration. Several studies have reported that 17 hydroxyprogesterone caproate injection can prevent recurrent PTB in women with a previous history of PTB. Vaginal micronized natural progesterone has also been shown to be effective in preventing PTB in women with previous PTB history or with a short CL. At present, we are performing a multi-center, randomized trial in Korea (a multicenter, randomized, open-label, investigator-initiated trial of vaginal compared with intramuscular progesterone for the prevention of PTB in high-risk pregnant women: VICTORIA protocol) to compare the efficacy between vaginal progesterone and intramuscular injection of progesterone in women with a previous preterm history or short CL. This study will provide important information to both obstetricians and patients on whether a vaginal or intramuscular regimen is better for prevention of a recurrent PTB.
17-alpha-Hydroxyprogesterone ; Female ; Humans ; Injections, Intramuscular ; Korea ; Parturition ; Pregnancy ; Pregnant Women ; Premature Birth* ; Progesterone* ; Progestins ; Recurrence ; Ultrasonography ; Victoria

No abstract available.
17-alpha-Hydroxyprogesterone*

An apparently well 27-year-old phenotypically male adult was seen at the endocrine clinic for gender assignment. Patient had been raised as a male and identifies as such. Abdominal CT scan showed a unilateral left adrenal mass and karyotyping revealed 46 XX female karyotype. She was diagnosed to have simple virilizing CAH and needed thorough counselling with subsequent management by a multidisciplinary team
17-alpha-Hydroxyprogesterone

Congenital adrenal hyperplasia is inherited disorder of adrenal steroidogenesis. 21-hydroxylase deficiency is the most commone enzymatic defect and is divided into classic and late-onset or nonclassic forms. Both classic non-classic 21-hydrozylase deficiencies are inherited in a recessive manner as allelic variants. But it is rare that happened in twin infants. Chief complaints of affected twins in our case were ambiguous genitalia, hyperpigmentation and dehydrations. They were revealed into hyponatremia, hyperkalemia and increased amount of serum progesterone, 17-hydroxyprogesterone and urinary 17-ketosteroid excretion and were administered with DOCA, 9alpha-fluorohydrocortisone, hydrocortisone to control the electrolyte imbalance. And now, both of them are going to normal ratio of weight gain and body growth.
17-alpha-Hydroxyprogesterone ; Adrenal Hyperplasia, Congenital* ; Desoxycorticosterone Acetate ; Disorders of Sex Development ; Humans ; Hydrocortisone ; Hyperkalemia ; Hyperpigmentation ; Hyponatremia ; Infant ; Progesterone ; Steroid 21-Hydroxylase* ; Twins* ; Weight Gain

Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most fatal form of CAH, as it disrupts adrenal and gonadal steroidogenesis. Most cases of lipoid CAH are caused by recessive mutations in the gene encoding steroidogenic acute regulatory protein (StAR). Affected patients typically present with signs of severe adrenal failure in early infancy and 46,XY genetic males are phenotypic females due to disrupted testicular androgen secretion. The StAR p.Q258X mutation accounts for about 70% of affected alleles in most patients of Japanese and Korean ancestry. However, it is more prevalent (92.3%) in the Korean population. Recently, some patients have been showed that they had late and mild clinical findings. These cases and studies constitute a new entity of 'nonclassic lipoid CAH'. The cholesterol side-chain cleavage enzyme, P450scc (CYP11A1), plays an essential role converting cholesterol to pregnenolone. Although progesterone production from the fetally derived placenta is necessary to maintain a pregnancy to term, some patients with P450scc mutations have recently been reported. P450scc mutations can also cause lipoid CAH and establish a recently recognized human endocrine disorder.
Alleles ; Asian Continental Ancestry Group ; Cholesterol ; Cholesterol Side-Chain Cleavage Enzyme ; Female ; Gonads ; Humans ; Hyperplasia* ; Male ; Placenta ; Pregnancy ; Pregnenolone ; Progesterone