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Fertility and Sterility Mar 1991The findings of our study indicate that women pretreated with E/progestin demonstrate increased gonadotropin requirements when undergoing ovulation induction. Whether... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The findings of our study indicate that women pretreated with E/progestin demonstrate increased gonadotropin requirements when undergoing ovulation induction. Whether this treatment has a significant effect on the outcome of ovulation induction in patients receiving gonadotropins remains to be established.
Topics: Adult; Chorionic Gonadotropin; Drug Therapy, Combination; Female; Follicle Stimulating Hormone; Humans; Menotropins; Mestranol; Norethindrone; Ovary; Ovulation Induction; Prospective Studies
PubMed: 1900488
DOI: 10.1016/s0015-0282(16)54203-4 -
Preventive Medicine Jan 1991Previously, we demonstrated that the synthetic estrogens mestranol and ethinyl estradiol (EE) were strong promoters of hepatocarcinogenesis initiated in intact female...
Previously, we demonstrated that the synthetic estrogens mestranol and ethinyl estradiol (EE) were strong promoters of hepatocarcinogenesis initiated in intact female rats by prior treatment with diethylnitrosamine (J. D. Yager, H. A. Campbell, D. S. Longnecker, B. D. Roebuck, and M. C. Benoit, Cancer Res. 1984; 44:3862-3869). In subsequent studies designed to elucidate possible mechanisms of promotion by EE, we investigated whether the antiestrogen tamoxifen was antagonistic to the effects of EE (J. D. Yager, B. D. Roebuck, T. L. Paluszcyk, and V. A. Memoli, Carcinogenesis 1986; 7:2007-2014). In these and more recent studies we found that tamoxifen inhibited the stimulatory effects of EE on pituitary size, liver DNA synthesis, and, in cultured hepatocytes, the potentiation by EE of epidermal growth factor-induced DNA synthesis. Furthermore, tamoxifen also inhibited the ability of EE to promote hepatocarcinogenesis. However, paradoxically, tamoxifen alone enhanced the appearance of gamma-glutamyl transpeptidase positive foci in diethylnitrosamine-initiated livers indicating that it is a promoter of hepatocarcinogenesis.
Topics: Animals; Carcinogens; DNA Replication; Diethylnitrosamine; Dose-Response Relationship, Drug; Drug Antagonism; Drug Evaluation, Preclinical; Drug Synergism; Epidermal Growth Factor; Ethinyl Estradiol; Female; Liver Neoplasms, Experimental; Organ Size; Pituitary Gland; Rats; Rats, Inbred Strains; Tamoxifen; gamma-Glutamyltransferase
PubMed: 1672563
DOI: 10.1016/0091-7435(91)90004-n -
Fertility and Sterility Nov 1990Estrogen (E)/progestin therapy for functional ovarian cysts is widely used in clinical practice, but the efficacy of this treatment has not been determined in controlled... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Estrogen (E)/progestin therapy for functional ovarian cysts is widely used in clinical practice, but the efficacy of this treatment has not been determined in controlled trials. In this study, we examined the effect of E/progestin administration in a group of infertility patients enrolled in a program of ovulation induction who had cysts identified by transvaginal sonography. Patients were randomized to receive either norethindrone 1 mg/mestranol 0.05 mg/d (group A, n = 24) or no treatment (group B, n = 24) for up to 6 weeks. Patients were re-evaluated by sonography at 3, 6, and 9 weeks after entry into the protocol. The ages, mean cyst diameters, and proportions of patients having received gonadotropins in the previous menstrual cycle were not significantly different among the two groups. All patients who had a sonographic abnormality persisting for 9 weeks were surgically explored and found to have pathological cysts. The rate of disappearance of functional ovarian cysts was not affected by E/progestin treatment.
Topics: Adult; Estrogens; Female; Humans; Infertility, Female; Ovarian Cysts; Progestins; Prospective Studies
PubMed: 2226910
DOI: No ID Found -
Fertility and Sterility Nov 1989
Topics: Administration, Intravaginal; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Contraceptives, Oral; Ethinyl Estradiol; Female; Hematologic Diseases; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Menstrual Cycle; Mestranol; Norethindrone; Stomatitis
PubMed: 2806624
DOI: No ID Found -
Fertility and Sterility Sep 1988The main conclusion of this study is that a profound suppression of the pituitary and ovary can be associated with an inadequate response which may require a longer or... (Comparative Study)
Comparative Study
The main conclusion of this study is that a profound suppression of the pituitary and ovary can be associated with an inadequate response which may require a longer or different regimen of stimulation to achieve the desired outcome for IVF. We suggest that a pretreatment determination of E2 and gonadotropins can be of value to predict the nature of ovarian response in women with suppressed pituitary-ovarian function.
Topics: Contraceptives, Oral; Contraceptives, Oral, Combined; Drug Combinations; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Mestranol; Norethindrone; Ovarian Follicle; Ovary; Pituitary Gland; Progesterone
PubMed: 3137106
DOI: No ID Found -
The American Journal of Pathology May 1988A total of 213 treated and 16 control monkeys comprising 12 experimental groups was evaluated for determination of the long-term (10 years) effects of various dosages of... (Comparative Study)
Comparative Study
The morphologic effects of synthetic reproductive steroids on the mammary gland of rhesus monkeys. Mestranol, ethynerone, mestranol-ethynerone, chloroethynyl norgestrel-mestranol, and anagestone acetate-mestranol combinations.
A total of 213 treated and 16 control monkeys comprising 12 experimental groups was evaluated for determination of the long-term (10 years) effects of various dosages of a variety of synthetic oral contraceptive steroids on the mammary glands of rhesus monkeys. The steroid hormones included mestranol, ethynerone, a combination of mestranol and ethynerone, chlorethynyl norgestrel plus mestranol, and anagestone acetate plus mestranol. Various degrees of physiologic lobular hyperplasia and lactational changes were observed in association with all of these steroid hormones; these changes appeared dose-dependent. Mestranol caused a proliferative atypia ranging from a minimal to a moderate degree in 8 of 34 (23%) animals, but it was not dose-related. Eleven of 15 monkeys (73%) administered ethynerone developed proliferative atypia, ranging in degree from minimal to severe, including one invasive carcinoma and 2 lesions resembling intraductal carcinoma in the human. The mestranol and ethynerone combination produced a proliferative atypia in 22 of 52 animals (42%), including five identical to intraductal carcinoma in the human and one identical to lobular neoplasia. Of the 40 monkeys administered anagestone acetate and mestranol, 20 (50%) developed proliferative atypias; the atypias ranged from mild to severe and included five resembling intraductal carcinoma in human breast. The chloroethynyl norgestrel and mestranol combination induced proliferative atypia in 25 of 52 monkeys (49%); six of these atypias were severe and indistinguishable from intraductal carcinoma of the human breast; and one, if in the human breast, would reflect a solid variant of an invasive carcinoma. Only 2 of the 16 control monkeys (12%) developed proliferative atypias, and these were of minimal to mild degree. The occurrence of severe degrees of atypia identical to intraductal carcinoma in the human breast and invasive carcinoma associated with hormone administration suggests a carcinogenic effect.
Topics: Animals; Drug Interactions; Estradiol Congeners; Female; Macaca mulatta; Mammary Glands, Animal; Mestranol; Norgestrel; Norpregnadienes; Pregnenes; Reference Values; Time Factors
PubMed: 3358452
DOI: No ID Found -
Journal of Lipid Research Jun 1986In an investigation of alterations in cholesterol metabolism during contraceptive steroid use, we studied plasma clearance of chylomicron remnants. Six healthy women...
In an investigation of alterations in cholesterol metabolism during contraceptive steroid use, we studied plasma clearance of chylomicron remnants. Six healthy women were studied on and off contraceptive steroid therapy. Remnant clearance was measured from the disappearance of retinyl palmitate administered intravenously in plasma endogenously labeled with retinyl palmitate. We also measured cholesterol in HDL and its subfractions and postheparin lipoprotein lipase and hepatic triglyceride lipase activities. Plasma decay of retinyl palmitate was biexponential. The rapid component, reflecting chylomicron remnant removal, accounted for about 90% of the total clearance in all studies. During contraceptive steroid intake, both rapid and slow decay constants and the calculated plasma clearance rates were significantly increased (mean values: rapid decay constant, control 0.048 versus treated 0.101 min-1, P less than 0.05; slow decay constant, 0.004 versus 0.014 min-1, P less than 0.01; plasma clearance 74 versus 115 ml/min, P less than 0.025) indicating enhanced hepatic uptake of chylomicron remnants and probably an increased hepatic uptake of higher density lipoproteins (d greater than 1.006 g/ml). Total postheparin lipolytic activity and lipoprotein lipase activity were depressed in all six women (P less than 0.05) and hepatic triglyceride lipase activity was increased in four of five subjects. Contraceptive steroids also caused a decrease in the HDL2/HDL3 cholesterol ratio (P less than 0.05), implying impaired peripheral lipoprotein triglyceride hydrolysis and/or increased HDL2 clearance by hepatic triglyceride lipase. In conclusion, during intake of contraceptive steroids, the plasma clearance of chylomicron remnants and higher density lipoproteins was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Biological Transport, Active; Cholesterol; Cholesterol, HDL; Chylomicrons; Contraceptives, Oral; Diterpenes; Female; Humans; Lipids; Liver; Metabolic Clearance Rate; Retinyl Esters; Vitamin A
PubMed: 3746133
DOI: No ID Found -
Infection and Immunity Apr 1986Subcutaneous infection chambers in rabbits were infected with a strain of Staphylococcus aureus isolated from a patient with toxic shock syndrome. Estrogens (mestranol...
Subcutaneous infection chambers in rabbits were infected with a strain of Staphylococcus aureus isolated from a patient with toxic shock syndrome. Estrogens (mestranol and 17-beta-estradiol) protected male rabbits and prolonged survival. Neither androgens (testosterone and dihydrotestosterone) nor progesterone affected the susceptibility of intact or ovarihysterectomized female rabbits.
Topics: Animals; Bacterial Toxins; Enterotoxins; Estradiol; Female; Gonadal Steroid Hormones; Male; Mestranol; Orchiectomy; Ovariectomy; Progesterone; Rabbits; Staphylococcus aureus; Superantigens; Testosterone
PubMed: 3957430
DOI: 10.1128/iai.52.1.331-333.1986 -
Fertility and Sterility Jun 1985Clinical and laboratory evaluations of nine hirsute women were performed for determination the efficacy of combination drug therapy. Each patient had previously failed...
Clinical and laboratory evaluations of nine hirsute women were performed for determination the efficacy of combination drug therapy. Each patient had previously failed to respond to single drug therapy with oral contraceptives (OC), dexamethasone (DEX), or spironolactone (S) and received S (100 to 150 mg) and either an OC (mestranol, 0.05 to 0.08 mg, and norethindrone, 1 mg) or DEX (0.5 mg) daily. Total testosterone, dehydroepiandrosterone sulfate, free testosterone, and sex-hormone-binding globulin were measured before therapy and 4 to 6 weeks after initiation of therapy and were compared with the responses to OC (n = 7), DEX (n = 8), and S (n = 6). A satisfactory clinical response in the rate of hair growth was defined as at least a doubling of the time interval between adjunctive therapies (electrolysis, shaving, or bleaching) and patient satisfaction with treatment. The responses of the androgenic parameters were not statistically different between combination and single drug therapy. Although all patients noted a subjective improvement in hair growth, eight of nine fulfilled the criteria for a clinical response (P less than 0.001). Transient diuresis was the only side effect noted. The study suggests that combination drug therapy is an efficacious and well-tolerated approach to the management of unresponsive hirsutism.
Topics: Contraceptives, Oral; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dexamethasone; Drug Therapy, Combination; Female; Hirsutism; Humans; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Spironolactone; Testosterone
PubMed: 3158552
DOI: No ID Found -
The Journal of Clinical Investigation Jun 1985To define the basis of the heterogeneity of angiotensinogen, we have characterized the immunoreactivity of high molecular weight (HMW) and low molecular weight (LMW)...
To define the basis of the heterogeneity of angiotensinogen, we have characterized the immunoreactivity of high molecular weight (HMW) and low molecular weight (LMW) plasma angiotensinogen, the angiotensinogen precursor synthesized by cell-free translation, and angiotensinogen secreted by human hepatoma (Hep G2) cells. Angiotensinogen precursor synthesized by rabbit reticulocyte lysate primed with RNA prepared from liver or Hep G2 cells was compared with angiotensinogen secreted by Hep G2 cells by using immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). So as to assess the contribution of N-glycosylation of angiotensinogen, Hep G2 cells were incubated in the presence of tunicamycin. Glycosylation of secreted angiotensinogen was further characterized by using chromatography on concanavalin A-Sepharose, digestion with neuraminidase, and treatment with trifluoromethane sulfonic acid. In Sephadex G-200 column chromatography, HMW plasma angiotensinogen eluted just after the column void volume and was clearly separated from LMW angiotensinogen which eluted just before bovine serum albumin. Both HMW and LMW plasma angiotensinogen were shown to bind to monoclonal and polyclonal antibodies raised against pure LMW angiotensinogen. Only one angiotensinogen precursor (mol wt 50,000) was identified by cell-free translation which, after cleavage by renin, was reduced to mol wt 45,600. Angiotensinogen secreted by Hep G2 cells showed electrophoretic heterogeneity (mol wt 53,100-65,400). Tunicamycin-treated Hep G2 cells secreted five discrete forms of angiotensinogen, a predominant form of mol wt 46,200, with other forms (mol wt 46,800, 48,100, 49,200, and 49,600) representing 10% of secreted angiotensinogen. All five forms showed a similar reduction in molecular weight after cleavage by renin. The predominant 46,200-mol wt protein represented nonglycosylated angiotensinogen in that, after cleavage by renin, it had an electrophoretic mobility (mol wt 45,600) identical to the desangiotensin I-angiotensinogen resulting from renin cleavage of the angiotensinogen precursor. The other higher molecular weight forms of angiotensinogen secreted by tunicamycin-treated Hep G2 cells were shown to represent O-glycosylated angiotensinogen in that they were reduced to 46,200 mol wt by treatment with trifluoromethane sulfonic acid. Dexamethasone (10(-7) and 10(-6)M) stimulated angiotensinogen secretion by Hep G2 cells two- to fourfold, both in the absence and presence of tunicamycin. However, a small stimulatory effect of mestranol (10(-7) M) was evident only in the presence of tunicamycin. Neither dexamethasone nor mestranol influenced the electrophoretic pattern (SDS-PAGE) of angiotensinogen secreted by Hep G2 cells. However, when incubation media were chromatographed on Sephadex G-200 with subsequent immunoprecipitation of the column fractions, both dexamethasone and mestranol were shown to stimulate the secretion of HMW angiotensinogen (eluting just after the column void volume) which, on SDS-PAGE, migrated in a position identical to LMW angiotensinogen. From these studies, we conclude that all forms of human angiotensinogen are derived from a single precursor. The heterogeneity of secreted angiotensinogen represents differences in posttranslational processing of angiotensinogen. This processing includes both N- and O-glycosylation, and also the formation of HMW complexes (HMW angiotensinogen) through association either with other angiotensinogen molecules or with some other protein(s) whose secretion by hepatocytes is stimulated by glucocorticoids and estrogens.
Topics: Angiotensinogen; Angiotensins; Animals; Antibodies, Monoclonal; Cells, Cultured; Dexamethasone; Glycoproteins; Humans; Liver Neoplasms, Experimental; Mestranol; Mesylates; Molecular Weight; Neuraminidase; Protein Precursors; RNA, Messenger; Secretory Rate; Tunicamycin
PubMed: 2989336
DOI: 10.1172/JCI111902