OBJECTIVES: To determine the baseline serum concentrations of estradiol and estrone in postmenopausal Korean women and the serum concentrations of estradiol and estrone after 4 and 16 weeks of treatment using 1 mg of estradiol and 2 mg of drospirenone. METHODS: This was a multicenter study. Thirty-six subjects were screened. Serum estradiol, estrone and drospirenone levels were determined by gas chromatography-mass spectrometry and radioimmunoassay. RESULTS: The mean estradiol concentration was 8.37 +/- 12.1 pg/mL at baseline and increased to 53.7 +/- 52.1 and 41.4 +/- 26.1 pg/mL after 4 and 16 weeks of treatment, respectively. The mean estrone concentrations were 28.7 +/- 26.8, 266.1 +/- 182.9, and 256.1 +/- 179.1 pg/mL at baseline, and after 4 and 16 weeks of treatment, respectively. When women were stratified according to the basal estradiol level, the level after 4 weeks of treatment was significantly higher in the women with a detectable level (> or = 5 pg/mL) than in women with an undetectable level (< 5 pg/mL; 65.2 +/- 21.5 vs. 37.4 +/- 25.8 pg/mL, P = 0.008). After 16 weeks of treatment, the estradiol level was still higher in the detectable group (51.6 +/- 28.6 vs. 38.7 +/- 21.7 pg/mL, P = 0.09). CONCLUSION: This study showed that 1 mg of estradiol and 2 mg of drospirenone is an appropriate regimen to achieve the desired serum estradiol level. The difference in serum hormonal levels after 4 weeks of treatment could be caused by different basal levels.
Administration, Oral ; Androstenes ; Estradiol ; Estrogen Replacement Therapy ; Estrone ; Female ; Gas Chromatography-Mass Spectrometry ; Humans ; Postmenopause

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

OBJECTIVETo identify the optimal dosage of 17beta-estradiol gel + oral progestin for preventing bone loss in postmenopausal Chinese women.

METHODSA 3-year open label, randomized, prospective clinical trial was conducted. Sixty healthy women who had been postmenopausal for 1 to 5 years were recruited and divided into following 4 groups: group 1, percutaneous gel 17beta-estradiol (E(2)) 1.5 mg/d plus micronized progesterone (MP) 100 mg/d; group 2, percutaneous gel 17beta-estradiol (E(2)) 1.5 mg/d plus medroxyprogesterone acetate (MPA) 2 mg/d; group 3, percutaneous gel 17beta-estradiol (E(2)) 0.75 mg/d plus micronized progesterone (MP) 100 mg/d; and group 4, percutaneous gel 17beta-estradiol (E(2)) 0.75 mg/d plus medroxyprogesterone acetate (MPA) 2 mg/d. Estrogen and progestin were given continuously for 25 days per month. Bone mineral density (BMD) was measured using quantitative computed tomography (QCT) for trabecular bone of L2-5 and dual energy X-ray absorptiometry (DEXA) for L2-4 and hip 5 times during the trial at baseline and at the 6-, 12-, 18-, 24- and 36-month visits.

RESULTSFifty-nine patients (98.3%, 59/60) stayed in the study for 1 year, 56 patients (93.3%, 56/60) for 2 years, and 51 (85%, 51/50) for 3 years. On average, menopausal symptoms were relieved by 80% after 6 months of treatment. By the 24th month, the mean increase in BMD ranged from 4.3% to 7.5% in trabecular bone; and by the 36th month, it ranged from 4.2% to 6.2% in L2-4 and 1.61% to 3.77% in the neck. There were significant difference after treatment (P < 0.05). Among the four groups, no significant difference (P > 0.05) was found in improvement of symptoms, levels of bone markers or BMD.

CONCLUSIONA daily dose of estradiol gel, either 0.75 mg or 1.5 mg, is effective in preventing early postmenopausal bone loss and relieving menopausal symptoms. After 3-year treatment, spinal BMD could increase steadily, so does hip BMD, especially in the first 2 years.

Administration, Cutaneous ; Adult ; Bone Density ; Estradiol ; administration & dosage ; Estrogen Replacement Therapy ; Female ; Fractures, Bone ; prevention & control ; Humans ; Medroxyprogesterone Acetate ; administration & dosage ; Middle Aged ; Osteoporosis, Postmenopausal ; prevention & control

OBJECTIVETo establish a stable animal model of azoospermia in male mice.

METHODSTwo groups of mice, with 30 in each, were intervened respectively by chemotherapy (intraperitoneal injection of Busulfan and Cyclophosphamide) and subcutaneous injection of Estradiol. At different times after the injection, the microscopic structures of the seminiferous tubules of both groups were observed and compared. The recovery of the germ cells in the seminiferous tubules was also evaluated after the termination of the intervention.

RESULTSA stable animal model was established by chemotherapeutic method with Busulfan and cyclophosphamide, while the model constructed by muscle injection of Estradiol was not stable.

CONCLUSIONCompared with estrogen injection, chemotherapeutic intervention is a reliable method for constructing an animal model of azoospermia in male mice.

Animals ; Azoospermia ; Busulfan ; administration & dosage ; Cyclophosphamide ; administration & dosage ; Disease Models, Animal ; Estradiol ; administration & dosage ; Injections, Intraperitoneal ; Injections, Subcutaneous ; Male ; Mice ; Mice, Inbred C57BL

OBJECTIVETo observe the clinical efficacy of warming Shen, enhancing Yang, invigorating qi, and nourishing blood method (WSEYIQNBM) combined artificial cycle therapy in treatment of premature ovarian failure (POF) patients of Shen yang deficiency syndrome (SYDS).

METHODSTotally 96 POF patients of SYDS were randomly assigned to the treatment group and the control group, 48 in each group. Patients in the treatment group were treated with WSEYIQNBM combined artificial cycle therapy, while those in the control group were treated with Western medicine artificial cycle therapy. One month constituted 1 course, a total of 3 courses. The menstruation and main symptoms were observed before and after treatment. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were detected before and after treatment.

RESULTSThe total effective rate was 85.43% in the treatment group, higher than that of the control group (79.17%, P < 0.05). Besides, better effect in improving Chinese medical symptoms was obtained in the treatment group (P < 0.05).

CONCLUSIONPOF patients' serum hormone levels and clinical symptoms could be improved by WSEYIQNBM combined artificial cycle therapy.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Estradiol ; administration & dosage ; therapeutic use ; Female ; Humans ; Phytotherapy ; Primary Ovarian Insufficiency ; diagnosis ; drug therapy

OBJECTIVETo investigate the value of serum estradiol increment and serum estradiol/follicles on the day of hCG administration in predicting the clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET).

METHODSA retrospective analysis of the IVF-ET data was conducted involving 121 patients who received a long gonadotrophin-releasing hormone agonist (GnRHa) protocol. According to the increment of serum estradiol on the day of hCG administration (relative to the level on the day before hCG administration), the patients were divided into 3 groups (A1, A2 and A3) with a increment ratio below 30%, between 30% and 50%, and over 50%, respectively. In addition, according to the ratio of serum estradiol level on hCG day to mature follicle (diameter ≥ 14 mm) number, these patients were divided into three groups (B1, B2 and B3) with the ratio below 250 pg/ml, between 250 and 350 gp/ml, and over 350 pg/ml, respectively. The hormonal characteristics and clinical outcomes of the IVF-ET cycles were analyzed comparatively.

RESULTSBoth the clinical pregnancy rate (71.05%) and embryo implantation rate (52.63%) were significantly higher in group A3 than in groups A1 and A2 (P<0.05). The best clinical pregnancy rate (67.86%) and embryo implantation rate (49.14%) were significantly higher in group B2 than in groups B1 and B3 (P<0.05).

CONCLUSIONThe variation of serum estradiol shows an important impact on the clinical outcomes of IVF-ET in patients receiving long GnRH-a protocol. Favorable outcomes can be expected with a hCG day serum estradiol increment ratio above 50% and E(2)/follicle ratio between 250 and 350 pg/ml.

Embryo Transfer ; Estradiol ; blood ; Female ; Fertility Agents, Female ; administration & dosage ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone ; administration & dosage ; agonists ; Humans ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To investigate the effect of estrogen replacement therapy (ERT) in the early phase on the atherosclerosis and the level of plasminogen activator inhibitor-1(PAI-1). METHODS: Twenty-eight rabbits were randomly assigned to 4 groups: Group A, sham operation (n=7); Group B, ovariectomized without estradiol (n=7); Group C, ovariectomized with low-dose estradiol (n=7); and Group D, ovariectomized with high-dose estradiol (n=7). All rabbits were given 1% cholesterol diet for 12 weeks. Levels of blood lipid, estradiol, and PAI-1 were measured before the operation and at the end of the 4th and 12th weeks. Twelve weeks later, we took the aortas for pathological analysis and calculated the areas of atherosclerotic plaque. RESULTS: After 12 weeks, the estradiol level of Group B was significantly lower than that of Group A, and that of Group D was obviously higher than Group A. There was no significant difference between Group C and A. The concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in Group B significantly increased compared with Group A (P<0.01). The levels of TC and LDL-C of Group C and D were significantly lower than those of Group A. Whereas the concentrations of triglyceride (TG) and high density lipoprotein cholesterol (HDL-C) in Group B were lower than those of Groups A, C and D (P<0.01). In contrast to Groups A, C and D, the level of PAI-1 was significantly higher in the Group B (P<0.01), without significant differences among Groups A, C and D. The area of atherosclerotic lesion of aorta in Group B was significantly bigger than that of Group A, C and D. The areas of aortic atherosclerotic plaque in Group C and D were obviously smaller than those of Group A (P<0.01). CONCLUSION Transdermal estrogen replacement therapy in the early phase can improve the metabolism of the serum lipids, reduce the level of PAI-1, and probably provide the protective effect on the atheroma formation.
Administration, Cutaneous ; Animals ; Atherosclerosis ; blood ; drug therapy ; pathology ; Cholesterol ; blood ; Estradiol ; administration & dosage ; Estrogen Replacement Therapy ; Female ; Ovariectomy ; Plasminogen Activator Inhibitor 1 ; blood ; Rabbits ; Triglycerides ; blood

This study was performed to analyze retrospectively outcomes of stimulated in vitro fertilization (IVF) cycles where the gonadotropin-releasing hormone (GnRH) antagonist was omitted on ovulation triggering day. A total of 92 consecutive IVF cycles were included in 65 women who are undergoing ovarian stimulation with recombinant FSH. A GnRH antagonist, cetrorelix 0.25 mg/day, was started when leading follicle reached 14 mm in diameter until the day of hCG administration (Group A, 66 cycles) or until the day before hCG administration (Group B, 26 cycles). The duration of ovarian stimulation, total dose of gonadotropins, serum estradiol levels on hCG administration day, and the number of oocytes retrieved were not significantly different between the two groups. The total dose of GnRH antagonist was significantly lower in Group B compared to Group A (2.7+/-0.8 vs. 3.2+/-0.9 ampoules). There was no premature luteinization in the subjects. The proportion of mature oocytes (71.4% vs. 61.7%) and fertilization rate of mature (86.3+/-19.7% vs. 71.8+/-31.7%) was significantly higher in Group B. There were no significant differences in embryo quality and clinical pregnancy rates. Our results suggest that cessation of the GnRH antagonist on the day of hCG administration during a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist without compromising IVF results.
Adult ; Chorionic Gonadotropin/administration & dosage ; Drug Administration Schedule ; Estradiol/blood ; Female ; Fertilization in Vitro ; Follicle Stimulating Hormone/administration & dosage/blood ; Gonadotropin-Releasing Hormone/*antagonists & inhibitors ; Hormone Antagonists/*administration & dosage ; Humans ; Ovulation Induction/*methods ; Recombinant Proteins/therapeutic use ; Retrospective Studies

OBJECTIVETo compare profiles and related factors of irregular bleeding induced by different types of low-dose hormone therapy (HT) and a Chinese formulated herbs products.

METHODSApplied with open-labeled, randomized, and clinical trial design, 136 postmenopausal women were assigned into four groups: group A: estradiol valerate (E2 V) 1 mg/d + medroxyprogesterone acetate (MPA) 2 mg/d; group B: conjugated equine estrogen 0.45 mg/d + MPA 2 mg/d; group C: tibolone 1.25 mg/d; group D: a Chinese formulated herbs product (Kuntai) 4# tid. Each subject took element calcium 400 mg/d and vitamin D 200 IU/d concomitantly. Modified Kupperman scores were assessed on baseline and every 3 months thereafter and irregular bleeding was recorded on menopausal diary every day. The duration of this study was 1 year. Results The efficacies were similar in three HT-managed groups, but was better than in group D, although the latter was also effective in alleviating menopausal symptoms. Hazard ratio (HR) of irregular bleeding was 1.00 in group C, 2.43 in group A (95% CI: 1.08-5.46), 3.12 in group B (95% CI: 1.42-6.88), and 0.73 in group D (95% CI: 0.26-2.04). Most cases initially experienced bleeding in the first 3 months but such initiation was a bit later in group C. Endometrium, as detected by B-mode ultrasound, increased approximately 1 mm in HT groups, while it was a bit thicker in group C. Long periods in reproductive age and short time since menopause were high risk factors for irregular bleeding.

CONCLUSIONProfiles of irregular bleeding in 3 commonly used types of low-dose HT are different and some factors such as long period in reproductive age and short time since menopause may contribute to bleeding initiation.

Adult ; Aged ; Double-Blind Method ; Estradiol ; administration & dosage ; analogs & derivatives ; Estrogen Replacement Therapy ; adverse effects ; Estrogens, Conjugated (USP) ; administration & dosage ; Female ; Humans ; Medroxyprogesterone Acetate ; administration & dosage ; Metrorrhagia ; etiology ; Middle Aged ; Norpregnenes ; administration & dosage ; Phytotherapy ; adverse effects ; Postmenopause ; Risk Assessment

Angioplasty, Balloon, Coronary ; Coronary Artery Bypass ; Coronary Disease ; therapy ; Drug Delivery Systems ; Estradiol ; administration & dosage ; Everolimus ; Humans ; Paclitaxel ; administration & dosage ; Sirolimus ; administration & dosage ; analogs & derivatives ; Stents ; adverse effects ; Tacrolimus ; administration & dosage