OBJECTIVES: Inflammation is a major mechanism underlying coronary heart disease (CHD) and C-reactive protein (CRP) is a marker of inflammation. When administered soon after menopause, menopausal hormone therapy (MHT) prevents CHD. This study was conducted to examine the impact of estrogen by administration route on CRP in postmenopausal Korean women using micronized progesterone (MP4) for endometrial protection. METHODS: This retrospective cohort study included 129 healthy women without CHD risk factors. Eighty-nine women took oral estrogen (conjugated equine estrogen, 0.625 mg/day or equivalent), and 40 women applied a 1.5-mg/day 0.1% percutaneous estradiol gel. MP4 was added in 82 women with an intact uterus. The CRP level was measured at baseline and three and six months after initiation of MHT. RESULTS: The baseline characteristics were comparable between the MHT groups except current age and age at menopause. After controlling for age, menopausal age, body mass index, and basal CRP, no significant change in CRP was observed in the oral estrogen group (n = 29). Follow-up CRP levels were also similar to the baseline in the percutaneous estrogen group (n = 18). However, three-month CRP was significantly lower than six-month CRP, and there was a significant time trend within the percutaneous estrogen group. However, the group difference did not reach statistical significance. CRP also did not differ by addition of MP4 in either group. CONCLUSIONS: In postmenopausal Korean women, no change in CRP was observed with oral estrogen, while percutaneous estrogen might decrease CRP. The estrogenic impacts were not influenced by adding MP4.
Body Mass Index ; C-Reactive Protein ; Cohort Studies ; Coronary Disease ; Drug Administration Routes ; Estradiol ; Estrogens ; Female ; Follow-Up Studies ; Hormone Replacement Therapy ; Humans ; Inflammation ; Menopause ; Postmenopause ; Progesterone ; Retrospective Studies ; Risk Factors ; Uterus

Ospemifene—a third-generation selective estrogen receptor modulator approved by the Food and Drug Administration in 2013—is an oral medication for the treatment of dyspareunia. In postmenopausal women with vulvovaginal atrophy, ospemifene significantly improves the structure and pH levels of the vagina, reducing dyspareunia. It is available as a 60-mg tablet; hence, women who may have had prior difficulty with vaginal administration or on-demand use of nonprescription lubricants and moisturizers would likely prefer this form of treatment. Preclinical studies demonstrated that ospemifene has an estrogen agonist action on the bone, reducing the cell proliferation of ductal carcinoma in an in situ model. Studies evaluating the safety of treatment for up to 52 weeks have shown that ospemifene is a safe medication with minimal impact on the endometrium. Further studies with larger number of subjects are necessary to better conclude its effects and long-term safety.
Administration, Intravaginal ; Atrophy* ; Carcinoma, Ductal ; Cell Proliferation ; Dyspareunia ; Endometrium ; Estrogens ; Female ; Humans ; Hydrogen-Ion Concentration ; Lubricants ; Menopause ; Selective Estrogen Receptor Modulators ; Tamoxifen ; United States Food and Drug Administration ; Vagina ; Vulva

Post-menopausal osteoporosis (PMO) is a major global human health concern. Owing to the need for therapeutic drugs without side effects, natural extracts containing various polyphenolic compounds that may exert estrogenic effects have been studied in depth. Rhus verniciflua Stokes (RVS), which has been used as a traditional herbal medicine for centuries in Korea, was recently revealed to exert estrogenic effects attributable to its bioactive ingredients sulfuretin and butein, which have strong estrogen receptor–binding affinities. In this study, the protective potential of RVS in PMO was evaluated by using an experimental animal model of PMO, which was established by ovariectomy (OVX) of female Sprague Dawley rats. The oral administration of RVS at 20 mg/kg or 100 mg/kg for 8 weeks markedly protected against OVX-induced atrophy of the uterine tube and reversed the elevation in the ratio of serum receptor activator of nuclear factor-κB ligand to osteoprotegerin, which is a marker of disease severity. In addition, RVS inhibited OVX-induced tibia bone loss, activated osteogenic activity, and suppressed osteoclastic activity in the tibial epiphyseal plate, a region of bone remodeling. Collectively, these factors indicated that the oral intake of RVS might be beneficial for the prevention of PMO.
Administration, Oral ; Atrophy ; Bone Remodeling ; Estrogens ; Fallopian Tubes ; Female ; Growth Plate ; Herbal Medicine ; Humans ; Korea ; Models, Animal ; Models, Theoretical* ; Osteoclasts ; Osteoporosis, Postmenopausal* ; Osteoprotegerin ; Ovariectomy ; Rats, Sprague-Dawley ; Rhus* ; Tibia

In female sexual dysfunction (FSD), psychological and contextual factors significantly influence organic components of sexual response and behavior. The hormonal environment also affects FSD. Therefore, a tailored medical approach to each individual's sexual symptom is inevitable. This paper reviews currently available pharmacological treatment of FSD including the most recent advances and future targets in pharmacotherapy. In hormonal therapies for FSD, efficacy of estrogens and androgens on the treatment of vaginal atrophy, low sexual desire, and small subsets of genital arousal disorder, respectively, have been demonstrated. However, we need more data regarding long-term safety. There are two non-hormonal agents approved by the US Food and Drug Administration. Flibanserin has shown marginal benefit over placebo for the treatment of hypoactive sexual desire disorder. Ospemifen has shown beneficial effect on vulvovaginal pain from hormone related atrophy although it requires a longer period data to assess safety in other female genital organs, such as uterus and ovaries. Controversies still remain regarding hormonal therapies for FSD. Besides, some of the developing drugs still require more reliable safety and efficacy data. However, pharmacologic treatment of FSD is a promising field yet to be explored.
Androgens ; Arousal ; Atrophy ; Drug Therapy ; Estrogens ; Female* ; Genitalia, Female ; Humans ; Ovary ; Sexual Dysfunctions, Psychological ; United States Food and Drug Administration ; Uterus

BACKGROUNDMenopausal hormone therapy (MHT) has been proven to have beneficial effects on several components of metabolic syndrome. However, the effects vary according to different regimens, dosages, and duration of MHT. The aim of the study was to evaluate the effect of standard-dose 0.625 mg conjugated equine estrogen (CEE) and half-dose 0.3 mg CEE daily with different progestogens in a continuous sequential regimen on postmenopausal metabolic parameters in generally healthy postmenopausal women.

METHODSA prospective, open-label, randomized controlled clinical trial was conducted between February 2014 and December 2015. Totally 123 Chinese postmenopausal women with climacteric symptoms were included in this study and were randomly assigned to three groups: Group A received CEE 0.3 mg/micronized progesterone (MP) 100 mg daily; Group B received CEE 0.625 mg/MP 100 mg daily; and Group C received CEE 0.625 mg/dydrogesterone 10 mg daily. Drugs were given in a continuous sequential pattern. The duration of treatment was 12 months. Clinical, anthropometrical, and metabolic variables were measured. Data were analyzed according to intention-to-treat analysis, using Student's t-test and analysis of variance.

RESULTSA total of 107 participants completed the 12-month follow-up and were included in the data analysis. At 12 months of treatment, high-density lipoprotein cholesterol and apolipoprotein A significantly increased, and low-density lipoprotein cholesterol, fasting glucose, and glycosylated hemoglobin significantly decreased in Groups B and C, compared with baseline (all P < 0.05). Among the three groups, only Group C showed significantly increased triglycerides compared with baseline (1.61 ± 0.80 mmol/L vs. 1.21 ± 0.52 mmol/L, P = 0.026). Each group showed a neutral effect on total cholesterol, lipoprotein A, apolipoprotein B, and fasting insulin levels. No cardiovascular and venous thromboembolic events occurred in the three groups.

CONCLUSIONSAmong Chinese postmenopausal women, half-dose CEE was not sufficient to induce a favorable lipid and carbohydrate profile compared with standard-dose CEE. Adding natural MP may counterbalance the TG-increasing effect of CEE.

TRIAL REGISTRATIONClinicalTrials.gov, NCT01698164; https://clinicaltrials.gov/ct2/show/NCT01698164?term=NCT01698164&rank=1.

Apolipoproteins B ; blood ; Blood Pressure ; drug effects ; Body Composition ; drug effects ; Dydrogesterone ; administration & dosage ; therapeutic use ; Estrogens, Conjugated (USP) ; administration & dosage ; therapeutic use ; Female ; Humans ; Insulin ; blood ; Lipoprotein(a) ; blood ; Metabolic Syndrome ; blood ; drug therapy ; Middle Aged ; Postmenopause ; Progesterone ; administration & dosage ; therapeutic use ; Triglycerides ; blood

Oseltamivir has been used as a worldwide preparation for treatment of influenza A and B including H1N1. Gastrointestinal discomforts as like nausea, vomiting are commonly reported but acute hemorrhagic colitis is a very rare adverse effect. We report a case of a 17-year-old male who showed abdominal pain, diarrhea and hematochezia after the second administration of oseltamivir. Computed tomography revealed continuous, circumferential and edematous wall thickening involving ascending to descending colon with pericolic infiltration. Colonoscopic examination revealed diffuse mucosal edema, congestion and friability, suggesting hemorrhagic colitis. Histopathological examination showed ischemia and focal loss of the crypts. It also showed hyalinization and minimal inflammatory cell infiltration in the lamina propria, consistent with acute to subacute ischemic colitis. This report is the first case of oseltamivir-related ischemic colitis proved by both endoscopic examination and pathologic findings in the patient who had no risk factor of ischemic colitis in Korea.
Abdominal Pain ; Administration, Oral* ; Adolescent ; Colitis* ; Colitis, Ischemic ; Colon, Descending ; Diarrhea ; Edema ; Estrogens, Conjugated (USP) ; Gastrointestinal Hemorrhage ; Humans ; Hyalin ; Influenza, Human ; Ischemia ; Korea ; Male ; Mucous Membrane ; Nausea ; Oseltamivir* ; Risk Factors ; Vomiting

OBJECTIVES: This study was conducted to examine the effects of hormone therapy on serum lipid levels in postmenopausal Korean women. METHODS: This retrospective cohort study included 154 healthy postmenopausal Korean women. Seventy-nine women took oral estrogen (conjugated equine estrogen 0.625 mg/day or equivalent), and 75 applied estrogen transdermally using 0.1% 17beta-estradiol gel. Micronized progesterone (MP) was added to 40 women of oral group and 49 women in transdermal group. Serum levels of triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and lipoprotein (a) were measured before, 3 and 6 month after hormone therapy. RESULTS: At baseline, mean body mass index (BMI) were lower (22.76 vs. 23.74 kg/m2) and proportion of family history of cardiovascular disease (CVD) (61 vs. 39%) were higher in oral group. In oral group, LDL-C and lipoprotein(a) levels decreased, and triglyceride and HDL-C levels increased significantly after 3 and 6 months. There was no significant change in lipoprotein levels compared to the baseline in transdermal group. There were also no differences with additional MP. Changing pattern of HDL-C during 6 months was significantly different by the route of estrogen administration. CONCLUSION: Oral estrogen therapy might be more beneficial than transdermal estrogen in terms of lipid in postmenopausal Korean women. The estrogen effects are not influenced by adding MP.
Body Mass Index ; Cardiovascular Diseases ; Cholesterol ; Cohort Studies ; Drug Administration Routes ; Estrogens ; Female ; Hormone Replacement Therapy ; Humans ; Lipoprotein(a) ; Lipoproteins ; Progesterone ; Retrospective Studies ; Triglycerides

Oestrogen is essential for maintaining bone mass, and it has been demonstrated to induce osteoblast proliferation and bone formation. In this study, complementary DNA (cDNA) microarrays were used to identify and study the expression of novel genes that may be involved in MC3T3-E1 cells' response to 17-β estradiol. MC3T3-E1 cells were inoculated in minimum essential media alpha (α-MEM) cell culture supplemented with 17-β estradiol at different concentrations and for different time periods. MC3T3-E1 cells treated with 10⁻⁸ mol⋅L⁻¹ 17-β estradiol for 5 days exhibited the highest proliferation and alkaline phosphatase (ALP) activity; thus, this group was chosen for microarray analysis. The harvested RNA was used for microarray hybridisation and subsequent real-time reverse transcription polymerase chain reaction (RT-PCR) to validate the expression levels for selected genes. The microarray results were analysed using both functional and pathway analysis. In this study, microarray analysis detected 5403 differentially expressed genes, of which 1996 genes were upregulated and 3407 genes were downregulated, 1553 different functional classifications were identified by gene ontology (GO) analysis and 53 different pathways were involved based on pathway analysis. Among the differentially expressed genes, a portion not previously reported to be associated with the osteoblast response to oestrogen was identified. These findings clearly demonstrate that the expression of genes related to osteoblast proliferation, cell differentiation, collagens and transforming growth factor beta (TGF-β)-related cytokines increases, while the expression of genes related to apoptosis and osteoclast differentiation decreases, following the exposure of MC3T3-E1 cells to α-MEM supplemented with 17-β estradiol. Microarray analysis with functional gene classification is critical for a complete understanding of complementary intracellular processes. This microarray analysis provides large-scale gene expression data that require further confirmatory studies.
3T3 Cells ; Alkaline Phosphatase ; drug effects ; Animals ; Apoptosis ; drug effects ; genetics ; Cell Culture Techniques ; Cell Differentiation ; drug effects ; genetics ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; genetics ; Collagen ; drug effects ; genetics ; Coloring Agents ; Cytokines ; drug effects ; genetics ; Estradiol ; administration & dosage ; pharmacology ; Estrogens ; administration & dosage ; pharmacology ; Gene Expression Profiling ; Mice ; Oligonucleotide Array Sequence Analysis ; Osteoblasts ; drug effects ; Signal Transduction ; drug effects ; genetics ; Tetrazolium Salts ; Thiazoles ; Transforming Growth Factor beta ; drug effects ; genetics

OBJECTIVES: Allergic rhinitis (AR) is a chronic upper respiratory tract disease that inflames the mucous membranes of the nose and occurs when circulating inflammatory cells including eosinophils and basophils migrate to and accumulate in the inflammation area by passing through the interstitium and capillary walls. To pass through these barriers, the inflammatory cells degrade extracellular matrix proteins. Matrix metalloproteinases (MMPs) released by inflammatory cells mediate the degradation of these proteins. MMPs have synthetic inhibitors and doxycycline, a tetracycline antibiotic, inhibits MMPs. This study investigated the efficiency of intranasal doxycycline in decreasing the symptoms and inflammatory cell infiltration in an animal model of AR. METHODS: AR was created in female Wistar rats by repeated intranasal challenge with ovalbumin by intraperitoneal injection. For 15 days, topical intranasal doxycycline was administered one hour before ovalbumin administration. Following intranasal administration, nasal symptoms were scored and the nasal mucosae of all rats were evaluated histopathologically. To investigate tissue changes, hematoxyline-eosin and Alcian blue/periodic acid Schiff stains were used. As well, cilia loss, goblet cell changes, vascular congestion, vascular proliferation, inflammatory cell infiltration, eosinophil infiltration and the degree of hypertrophy in chondrocytes were evaluated with light microscopy. RESULTS: Typical symptoms of AR were decreased by intranasal doxycycline administration. These effects were stable after repeated intranasal ovalbumin administration. Histological evaluation of doxycycline treated rats did not reveal typical inflammatory changes associated with AR. CONCLUSION: MMPs may have crucial functions in AR and topical intranasal doxycycline, which decreases inflammatory cell infiltration, may offer an alternative therapy for AR.
Administration, Intranasal ; Animals ; Basophils ; Capillaries ; Chondrocytes ; Cilia ; Coloring Agents ; Doxycycline* ; Eosinophils ; Estrogens, Conjugated (USP) ; Extracellular Matrix Proteins ; Female ; Goblet Cells ; Humans ; Hypertrophy ; Inflammation ; Injections, Intraperitoneal ; Matrix Metalloproteinase Inhibitors ; Matrix Metalloproteinases ; Microscopy ; Models, Animal ; Mucous Membrane ; Nasal Mucosa ; Nose ; Ovalbumin ; Rats* ; Rats, Wistar ; Respiratory Tract Diseases ; Rhinitis* ; Tetracycline

OBJECTIVETo observe the effects of low-dose exogenous estrogen nonylphenol (NP) on the proliferation of human prostate cancer cell lines DU-145 and the expression of the membrane estrogen receptor GPR30 in the DU-145 cells.

METHODSWe exposed DU-145 cells to different concentrations of NP for 24 hours, followed by measurement of the half maximal inhibitory concentration (IC50) of the cells by cell proliferation assay and determination of the concentration of exposure to low-dose NP. We also observed the expressions of 3 estrogen receptors (ER), including ER-alpha, ER-beta and membrane estrogen receptor GPR30, in the DU-145 cells exposed to low-dose NP by RT-PCR.

RESULTSCell proliferation assay showed that within a certain range of doses, NP inhibited the proliferation of the DU-145 cells with an IC50 of 46 micromol/L, a much lower dose of NP than IC50, 0.01, 0.1.1 micromol/l NP, that can promote the proliferation of DU-145 cells. The results of RT-PCR indicated that the expressions of the three ERs in the DU-145 cells were similar to those in prostate epithelial cells, and that low-dose NP promoted the expression of GPR30.

CONCLUSIONMembrane estrogen receptor GPR30 may play a role in low-dose NP promoting the proliferation of DU-145 cells.

Cell Line, Tumor ; Cell Proliferation ; drug effects ; physiology ; Estrogen Receptor alpha ; metabolism ; Estrogen Receptor beta ; metabolism ; Estrogens ; Humans ; Male ; Phenols ; administration & dosage ; pharmacology ; Prostatic Neoplasms ; metabolism ; pathology ; Receptors, Estrogen ; metabolism ; Receptors, G-Protein-Coupled ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction