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Fertility and Sterility Dec 2004We describe the in vivo features of endometrium stained with methylene blue dye and observed via microhysteroscopy, showing the patterns of endometrial glands and...
We describe the in vivo features of endometrium stained with methylene blue dye and observed via microhysteroscopy, showing the patterns of endometrial glands and superficial cell changes during the midproliferative, periovulatory, and midluteal phases. These preliminary observations have allowed us to identify a series of changes occurring in the different phases of the ovulatory cycle of potential value in reproductive medicine for specific groups of infertile patients.
Topics: Cervix Uteri; Coloring Agents; Contraceptives, Oral, Combined; Endometrium; Ethynodiol Diacetate; Female; Follicular Phase; Humans; Hysteroscopy; Injections; Luteal Phase; Mestranol; Methylene Blue; Reference Values; Staining and Labeling
PubMed: 15589887
DOI: 10.1016/j.fertnstert.2004.07.947 -
Epilepsia Apr 2003To study the pharmacokinetics of a combination oral contraceptive (OC) containing norethindrone and ethinyl estradiol during OC monotherapy, concomitant OC and... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects.
PURPOSE
To study the pharmacokinetics of a combination oral contraceptive (OC) containing norethindrone and ethinyl estradiol during OC monotherapy, concomitant OC and topiramate (TPM) therapy, and concomitant OC and carbamazepine (CBZ) therapy in order to comparatively evaluate the pharmacokinetic interaction, which may cause contraceptive failure.
METHODS
This randomized, open-label, five-group study included two 28-day cycles. Five groups of female subjects received oral doses of ORTHO-NOVUM 1/35 alone (cycle 1) and then concomitant with TPM or CBZ (cycle 2). The treatment groups were group 1, TPM, 50 mg/day; group 2, TPM, 100 mg/day; group 3, TPM, 200 mg/day; group 4, TPM, 200 mg/day (obese women); and group 5, CBZ, 600 mg/day. Group 4 comprised obese women whose body mass index (BMI) was between 30 and 35 kg/m(2). The BMI of the remaining four groups was < or =27 kg/m2.
RESULTS
Coadministration of TPM at daily doses of 50, 100, and 200 mg (nonobese) and 200 mg (obese) nonsignificantly (p > 0.05) changed the mean area under the curve (AUC) of ethinyl estradiol by -12%, +5%, -11%, and -9%, respectively, compared with OC monotherapy. A similar nonsignificant difference was observed with the plasma levels and AUC values of norethindrone (p > 0.05). CBZ (600 mg/day) significantly (p < 0.05) decreased the AUC values of norethindrone and ethinyl estradiol by 58% and 42%, respectively, and increased their respective oral clearance by 69% and 127% (p < 0.05). Because CBZ induces CYP 3A-mediated and glucuronide conjugation metabolic pathways, the significant increase in the oral clearance of ethinyl estradiol and norethindrone was anticipated.
CONCLUSIONS
TPM, at daily doses of 50-200 mg, does not interact with an OC containing norethindrone and ethinyl estradiol. The lack of the TPM-OC interaction is notable when it is compared with the CBZ-OC interaction.
Topics: Administration, Oral; Adult; Anticonvulsants; Area Under Curve; Body Mass Index; Carbamazepine; Contraceptives, Oral, Combined; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Interactions; Enzyme Induction; Ethinyl Estradiol; Female; Fructose; Humans; Mestranol; Metabolic Clearance Rate; Norethindrone; Obesity; Topiramate
PubMed: 12681003
DOI: 10.1046/j.1528-1157.2003.55602.x -
Bioscience, Biotechnology, and... Jul 2002In this study, we investigated the estrogenic activity of environmental estrogens by a competition binding assay using a human recombinant estrogens receptor (hERbeta)...
In this study, we investigated the estrogenic activity of environmental estrogens by a competition binding assay using a human recombinant estrogens receptor (hERbeta) and by a proliferation assay using MCF-7 cells and a sulforhodamine-B assay. In the binding assay, pharmaceuticals had a stronger binding activity to hERbeta than that of some phytoestrogens (coumestrol, daidzein, genistein, luteolin, chrysin, flavone, and naringenin) or industrial chemicals, but phytoestrogens such as coumestrol had a binding activity as strong as pharmaceuticals such as 17alpha-ethynylestradiol (EE), tamoxifen (Tam), and mestranol. In the proliferation assay, pharmaceuticals such as diethylstilbestrol, EE, Tam, and clomiphene, and industrial chemicals such as 4-nonylphenol, bisphenol A, and 4-dihydroxybiphenyl had a proliferation-stimulating activity as strong as 17beta-estradiol (ES). In addition, we found that phytoestrogens such as coumestrol, daidzein, luteolin, and quercetin exerted a proliferation stimulating activity as strong as ES. Furthermore, we examined the suppression of proliferation-stimulating activity, induced by environmental estrogen, by flavonoids, such as daidzein, genistein, quercetin, and luteolin, and found that these flavonoids suppressed the induction of the proliferation-stimulating activity of environmental estrogens. The suppressive effect of flavonoids suggests that these compounds have anti-estrogenic and anti-cancer activities.
Topics: Binding, Competitive; Breast Neoplasms; Charcoal; Enzyme-Linked Immunosorbent Assay; Estrogen Antagonists; Estrogens, Non-Steroidal; Female; Flavonoids; Gonadal Steroid Hormones; Humans; Receptors, Estrogen; Recombinant Proteins; Tumor Cells, Cultured
PubMed: 12224631
DOI: 10.1271/bbb.66.1479 -
Fertility and Sterility Oct 2001To longitudinally evaluate disturbances of the hypothalamic-pituitary-adrenal (HPA) axis in women with secondary progestin-negative hypothalamic amenorrhea.
OBJECTIVE
To longitudinally evaluate disturbances of the hypothalamic-pituitary-adrenal (HPA) axis in women with secondary progestin-negative hypothalamic amenorrhea.
DESIGN
Retrospective cohort study.
SETTING
Yokohama City University, Yokohama, Japan.
PATIENT(S)
Twenty-four women with progestin-negative hypothalamic amenorrhea.
INTERVENTION(S)
Administration of human corticotropin-releasing hormone (hCRH) and treatment with a combination of estrogen and progesterone.
MAIN OUTCOME MEASURE(S)
Plasma cortisol and ACTH concentrations and period required for recovery from amenorrhea.
RESULT(S)
Plasma ACTH concentrations 30 and 60 minutes after injection of hCRH and the percent maximum increment (%Cmax) of ACTH were significantly lower in the amenorrheic patients compared with the control group patients. The basal cortisol was significantly higher, and the %Cmax of cortisol was significantly lower. In the 16 patients who recovered from amenorrhea, there was a significant positive correlation (Y = 1.93X-10.8, r = 0.629) between the basal cortisol concentrations (X) and the period for recovery (Y). The serum E2 gradually increased before recovery, and this E2 increase was preceded by changes in the plasma cortisol concentration and the %Cmax values of cortisol and ACTH.
CONCLUSION(S)
The CRH test might be useful for evaluating the roles of stress and for estimating the period required for recovery in hypothalamic amenorrhea.
Topics: Adrenocorticotropic Hormone; Adult; Amenorrhea; Corticotropin-Releasing Hormone; Estradiol Congeners; Female; Humans; Hydrocortisone; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Longitudinal Studies; Mestranol; Norethindrone; Pituitary-Adrenal System; Progesterone Congeners; Progestins; Reference Values; Time Factors
PubMed: 11591409
DOI: 10.1016/s0015-0282(01)02000-3 -
Clinical and Diagnostic Laboratory... Jul 2001Splenic-macrophage Fcgamma receptors (FcgammaRs) participate in the pathophysiologies of immune-complex diseases and in host defense against infection. Modulation of...
Splenic-macrophage Fcgamma receptors (FcgammaRs) participate in the pathophysiologies of immune-complex diseases and in host defense against infection. Modulation of macrophage FcgammaR expression is an immuno-therapeutic target. Glucocorticoids, sex steroids, and dopaminergic drugs modulate macrophage FcgammaR expression. Previous data indicate that estradiol increases macrophage FcgammaR expression. Nevertheless, the effects of clinically used estrogens upon macrophage FcgammaR expression are unknown. We assessed the effects of treatment with commonly used estrogens on the expression of macrophage FcgammaRs using a guinea pig experimental model. Six estrogens have been studied: ethynylestradiol (Et), mestranol (M), chlortianisene (Ct), promestriene, 17-epiestriol, and 17beta-estradiol. Following in vivo treatment of guinea pigs, we determined the clearance of immunoglobulin G (IgG)-sensitized erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic-macrophage FcgammaR cell surface expression. Estrogens enhance the clearance of IgG-sensitized erythrocytes by increasing splenic-macrophage FcgammaR expression. Et, M, and Ct were more effective than the other estrogens. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that estrogens increase the cell surface expression of FcgammaR1 and -2 more than that of FcgammaR2. These data indicate that treatment with commonly used estrogens enhances the clearance of IgG-sensitized cells by improving splenic-macrophage FcgammaR expression.
Topics: Animals; Erythrocytes; Estrogens; Guinea Pigs; Macrophages; Male; Receptors, IgG; Spleen
PubMed: 11427431
DOI: 10.1128/CDLI.8.4.806-810.2001 -
BMJ (Clinical Research Ed.) Sep 1997
Topics: Cardiovascular Diseases; Estradiol Congeners; Estrogen Replacement Therapy; Female; Humans; Mestranol; Meta-Analysis as Topic; Odds Ratio
PubMed: 9310579
DOI: No ID Found -
Endocrine Journal Oct 1996A female infant with partial androgen insensitivity (PAIS) was first seen at 4 months of age with slight virilization of the genitalia and externally palpable testes....
Incomplete testicular feminization syndrome: studies on androgen receptor(AR) function, AR gene analysis, and aromatase activities at puberty and long-term observations of clinical and hormonal features from infancy to puberty.
A female infant with partial androgen insensitivity (PAIS) was first seen at 4 months of age with slight virilization of the genitalia and externally palpable testes. Sex chromosome was 46,XY. She received left orchidectomy and exploratory laparotomy at 2 yr of age. At exploratory laparotomy, neither a uterus nor fallopian tubes were found. The right testis was preserved by fixing it at the external inguinal ring expecting spontaneous pubertal maturation. After discharge, serum levels of LH, FSH, testosterone (T) and estradiol (E2) were measured annually, and the steroid responses to hCG stimulation were examined every two yr. At the age of 10 yr, she developed breasts and a very feminine body habitus. At 12 yr, she received a clitoroplasty and right orchidectomy. The fibroblast cultures were made from the genital skin whereby androgen receptor (AR) binding was assessed by radioreceptor assay using 3H-DHT as the ligand, and thermoinstability of AR was noted despite normal maximum binding (Bmax) and dissociation constant (Kd) at 22 degrees C. But another binding experiment with 3H-Mibolerone resulted in the lack of receptor binding. AR gene analysis with direct sequencing of coding exons of the gene revealed no abnormality of the AR gene. 5 alpha-reductase activity was normal. Aromatase activity appeared to be enhanced in the genital skin fibroblast (GSF) cells as well as in the testicular tissue. The results of these studies indicated that the patient had PAIS with impaired AR functions and increased aromatase activity. After the discharge, the patient has maintained feminine phenotype, receiving estrogen therapy with mestranol 0.02 mg/day po.
Topics: Aging; Androgen-Insensitivity Syndrome; Aromatase; Cells, Cultured; Child; Chorionic Gonadotropin; Estradiol; Female; Fibroblasts; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Humans; Luteinizing Hormone; Male; Puberty; Receptors, Androgen; Reference Values; Syndrome; Testis; Testosterone
PubMed: 8980896
DOI: 10.1507/endocrj.43.557 -
Preventive Medicine Mar 1993Case-control studies of oral contraceptive use and breast cancer have used neighborhood, population, or hospital controls.
BACKGROUND
Case-control studies of oral contraceptive use and breast cancer have used neighborhood, population, or hospital controls.
METHODS
To determine whether this association differs according to type of controls, interview data from 131 incident cases of breast cancer were compared with those of 189 hospital controls and 182 neighborhood controls Study subjects were white females recruited between 1973 and 1975 from among residents of Baltimore City and County ages 18 to 59 years.
RESULTS
Adjusted relative odds of breast cancer related to ever versus never use of oral contraceptives were 1.0 and 0.8, using hospital and neighborhood controls, respectively. Relative odds did not increase proportionally to duration of oral contraceptive use or to progestogen potency. Although few subjects had used oral contraceptives for more than 2 years, almost all pill brands contained more than 49 micrograms of ethinyl estradiol or of mestranol.
CONCLUSIONS
Results from the present study do not support the hypothesis that early preparations of oral contraceptives increased breast cancer risk among white women, regardless of whether controls are neighbors of the cases or hospital patients. However, its conclusions cannot be generalized to women who began taking the pill before their first full-term birth or took it for more than 2 years.
Topics: Adolescent; Adult; Age Factors; Breast Neoplasms; Case-Control Studies; Contraceptives, Oral; Dose-Response Relationship, Drug; Educational Status; Ethinyl Estradiol; Female; Humans; Maryland; Matched-Pair Analysis; Mestranol; Middle Aged; Odds Ratio; Research Design; Time Factors
PubMed: 8483857
DOI: 10.1006/pmed.1993.1015 -
Japanese Journal of Cancer Research :... Jun 1992The present study reports the modulatory influences of combined oral contraceptive formulations, Ovral (0.05 mg ethinylestradiol plus 0.5 mg norgestrel per pill) and...
The present study reports the modulatory influences of combined oral contraceptive formulations, Ovral (0.05 mg ethinylestradiol plus 0.5 mg norgestrel per pill) and Noracycline (0.05 mg ethinylestradiol plus 0.1 mg lynestrenol per pill), on methylcholanthrene (MCA)-induced carcinogenesis in the uterine cervix of Swiss albino mouse. Placement of cotton thread impregnated with beeswax containing approximately 300 micrograms of MCA yielded cervical tumors in 0.0%, 8.6% and 26% animals, respectively, in 30, 60 and 90 days. Concomitant treatments with doses D1 (1/2000th of a pill), D2 (1/200th of a pill) and D3 (1/20th of a pill) of Ovral yielded cervical tumors in 0.0%, 0.0% and 4.5% mice at 30 days, 0.0%, 6.2% and 10% mice at 60 days and in 3.3% (P less than 0.05), 3.4% (P less than 0.05) and 47% mice at 90 days, respectively. Likewise, concomitant treatments with doses D1 (1/2000th of a pill), D2 (1/200th of a pill) and D3 (1/20th of a pill) of Noracycline yielded cervical tumors in 0.0%, 0.0%, 16.6% mice at 30 days, 4%, 3.7% and 54% (P less than 0.05) mice at 60 days and 3.2% (P less than 0.05), 20% and 63% (P less than 0.05) of mice at 90 days, respectively. Both Ovral and Noracycline displayed biphasic action on MCA-induced cervical carcinogenesis in mice. At lower dose levels (D1 and D2), they were inhibitory while at the higher dose level (D3) they were augmentatory in their actions. Both pills also significantly enhanced the incidence of cervical hyperplasia.
Topics: Animals; Body Weight; Carcinoma, Squamous Cell; Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Dose-Response Relationship, Drug; Drug Combinations; Ethinyl Estradiol; Ethinyl Estradiol-Norgestrel Combination; Female; Lynestrenol; Mestranol; Methylcholanthrene; Mice; Norgestrel; Precancerous Conditions; Uterine Cervical Diseases; Uterine Cervical Neoplasms
PubMed: 1644661
DOI: 10.1111/j.1349-7006.1992.tb00128.x -
British Journal of Cancer Jan 1992Data on 2,754 cases and 18,565 controls from a multinational hospital-based, case-control study were analysed to determine whether observed associations between combined... (Clinical Trial)
Clinical Trial Comparative Study
Data on 2,754 cases and 18,565 controls from a multinational hospital-based, case-control study were analysed to determine whether observed associations between combined oral contraceptives and breast cancer are similar for oral contraceptives with varying types and doses of oestrogens and progestins. After stratifying on duration of use, risk was found to be increased in current and recent users, and to decline with time since last use. These associations, of similar strength, were observed for users of products that contain mestranol and ethinyl estradiol, for women who used preparations with progestins derived from 19-nortestosterone and 17-alpha-hydroxyprogesterone, and for those who took preparations with relatively higher and lower doses of oestrogen. When products with equal doses of the same oestrogen or progestin and varying doses of the other hormonal constituent were considered, slightly higher relative risks per year of use were estimated for users of products with relatively higher than lower doses of either the constituent oestrogen or progestin, but the differences in relative risk could readily have occurred by chance. This study provides no evidence that risk of breast cancer in users of oral contraceptives varies by the type of oestrogen or progestin consumed.
Topics: Breast Neoplasms; Case-Control Studies; Contraceptives, Oral, Combined; Estrogens; Female; Humans; Progestins; Risk Factors; Time Factors; World Health Organization
PubMed: 1733433
DOI: 10.1038/bjc.1992.20