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At least 19 recordsLinked to original sources
PubMed2006

Effects of oral contraceptive, synthetic progestogen or natural estrogen pre-treatments on the hormonal profile and the antral follicle cohort before GnRH antagonist protocol.

BACKGROUND: Steroid pre-treatments may be useful to program GnRH antagonist IVF/ICSI cycles. This prospective study assessed hormonal and ultrasound data collected during the free period after the discontinuation of three different pre-treatments to provide information on the optimal time interval required before starting stimulation. METHODS: Women were randomized to receive oral contraceptive pill (OCP) [ethinyl estradiol (E(2)) 30 microg + desogestrel 150 microg] (n = 21) or norethisterone 10 mg/day (n = 23) or 17-betaE(2) 4 mg/day (n = 25) or no pre-treatment (n = 24) for one cycle before IVF. Assessments were performed on post-treatment day (PD) 1, 3 and 5, or on spontaneous cycle day (CD) 1 and 3. RESULTS: After OCP and progestogen administration, FSH and LH concentrations shifted from strongly suppressed PD1 levels to PD5 values similar to those observed on CD1. Meanwhile, follicle sizes remained small up to PD5. In contrast, estrogen pre-treatment poorly reduced FSH levels on PD1 compared with OCP or progestogen. Consequently, follicle size was more heterogeneous. FSH rebound was maximal on PD3, whereas LH levels were slightly increased up to PD5. CONCLUSIONS: A 5-day free interval after OCP or progestogen offers the advantages of gonadotrophin recovery and homogeneous follicular cohort, whereas early FSH rebound occurring after estrogen pre-treatment argues for a short free period.

Adult↗
PubMed1983

Embryotoxicity of Norlestrin, a combined synthetic oral contraceptive, in rhesus macaques (Macaca mulatta).

Thirty timed-mated pregnant rhesus monkeys received Norlestrin (Norethindrone acetate, 2.5 mg, and ethinyl estradiol, 0.05 g per tablet, Parke-Davis) orally at four different dose levels. The dose levels were 5, 10, 25 and 50 mg/day/monkey and the doses were administered during early (days 21-35), late (days 33-46), and throughout (days 21-46) organogenesis, except for the 50-mg-dose-group animals, which were treated only during early organogenesis (days 21-35). All except the animals in the 60-mg-dose group were allowed to go to term (165 days gestation). Pregnancy for the animals in the 50-mg-dose group was terminated by cesarean section on day 50 of gestation and the fetuses were fixed, serially sectioned, and examined histologically. No teratogenicity was observed. However, the prenatal mortality rate (38.5%) was higher for the Norlestrin-treated animals than in the control colony (21%). Eight animals aborted between days 40 and 78 of gestation and two other cases resulted in stillbirths at 139 and 165 days of gestation. There was a higher incidence of abortion (44.4%) in the 25-mg-dose group. Norlestrin treatment during early organogenesis also resulted in a higher abortion rate (37.5%) compared to treatment during late organogenesis (22.2%) abortions). No morphological abnormalities were found in infants observed at birth or in juvenile monkeys which died of natural causes or in those that were sacrificed over a period of two years. No histopathology was observed in the 50-day-old fetuses examined by serial section. Examination of endogenous maternal serum estrogen and progesterone levels in Norlestrin-treated monkeys (25 mg/day, days 21-35) suggested that placental steroidogenesis was not affected; however, the lower levels of estrogen in maternal serum suggested that the ovarian steroidogenesis was affected. Although the precise pathogenesis of this selective embryolethality is not known, several observations in this study suggest a direct generalized embryotoxic effect. Thus, this study for the first time has demonstrated that, while Norlestrin may be embryolethal at 100 times the human contraceptive dose equivalent (25 mg/day) in the rhesus monkey, nevertheless it does not affect the offspring which survive the exposure.

Abortion, Spontaneous↗
PubMed1977

Influence of oral contraceptives on the acute effect of amphetamine on the hepatic endoplasmic reticulum of the rat.

The interaction between amphetamine and synthetic oral contraceptive steroids have been studied in the female rat. A progestational agent, quingestanol acetate, and a standard combination contraceptive (quingestanol acetate/ethynyl estradiol) were given with and without the concurrent administration of amphetamine. Steroid treatments increased the activity of some drug-metabolizing enzymes (aminopyrine N-demethylase, coumarin 3- hydroxylase, hexobarbital oxidase). Other parameters measured remained unaltered (glucose-6-phosphatase, aniline hydroxylase, cytochrome c reductase, cytochrome P 450, microsomal protein and phospholipid contents). Amphetamine treatment alone raised some drug-metabolizing enzymes (coumarin 3-hydroxylase, hexobarbital oxidase), increased microsomal phospholipid content and de novo synthesis, but elicited no effect on other enzymes measured. Amphetamine and quingestanol acetate given together significantly increased some drug metabolizing enzymes while the simultaneous treatment with combined steroids and amphetamine showed the most pronounced action. These experiments thus revealed that at least in the liver of the female rat, amphetamine elicited no overt hepatotoxicity, rather, brought about a weak inductive action of drug metabolizing enzymes. The application of steroid hormones also raised drug metabolism and the interaction between amphetamine and contraceptive steroids showed additive effects.

Animals↗
PubMed1983

Effect of synthetic oestrogens and progestagens in oral contraceptives on bile lipid composition.

The prevalence of cholesterol gall stones in young women has increased since the introduction of oral contraceptives. The synthetic female sex hormones used in these preparations, increase the degree of cholesterol saturation in bile. To determine whether oestrogens, progestagens, or both, are responsible for the change in biliary cholesterol saturation index, a prospective randomised, controlled study was performed. A significant increase in the cholesterol saturation index of bile was observed when either 30 micrograms ethinyloestradiol plus 150 micrograms norgestrel (p = 0.01) or 50 micrograms ethinyloestradiol plus 250 micrograms norgestrel (p less than 0.01) were ingested daily for two months. No change in the cholesterol saturation index was observed when 30 micrograms ethinyloestradiol alone, or 30 micrograms ethinyloestradiol plus 2.5 mg norethisterone were used. The mechanism for the increase in cholesterol saturation index did not appear to involve bile acid metabolism. These results indicate that the progestagen, norgestrel, and not as previously thought the oestrogen, ethinyloestradiol, is responsible for the increase in cholesterol saturation of bile which accompanies the use of oral contraceptives.

Adult↗
PubMed1981

Sex hormone binding globulin: effect of synthetic steroids on the assay and effect of oral contraceptives.

The effect that synthetic steroid components of different oral contraceptives have on the assay system for measurement of sex hormones binding globulin (SHBG)-binding capacity, has been examined. Interference with the assay was not demonstrable at therapeutic levels of the drugs. d-Norgestrel was the only steroid studied which bound to SHBG with an affinity comparable to the endogenous sex hormones; it also tended to decrease SHBG-finding capacity, whereas preparations containing low levels of norethisterone increased the binding capacity. We suggest that measurement of changes in SHBG-binding capacity in subjects taking oral contraceptives may prove useful in indicating changes in sex hormone balance, particularly in view of the well-recognised side-effect of these drugs.

Contraceptives, Oral↗
PubMed1986

Biological activity of oral contraceptives.

The synthetic steroid hormones used in oral contraceptives differ in their effects and potencies. Because all low-dose preparations currently sold in the United States contain the same estrogen, the differences among progestin components are of clinical significance. Synthetic progestins may have progestational, estrogenic, antiestrogenic, and androgenic effects; all have antiovulatory effects. Means for measuring the different effects of steroid hormones, ranging from animal assays to human studies, are reviewed. The problems of generalizing from effects of one steroid in an animal system to combination steroids in the human system are emphasized. Our evolving concept of desirable and undesirable effects of progestins is reviewed, the concept of minimal effective dose introduced, and a conclusion suggested from the limited human data available. A plan for the selection of contraceptive steroids for human use is proposed.

Animals↗
PubMed1983

The effects of oral contraceptives on respiration.

The effect synthetic progestins found in current oral contraceptives may exert on respiratory function has not been thoroughly investigated. This study monitored potential changes in respiratory parameters 3 and 6 months subsequent to beginning administration. Static and timed spirometric maneuvers showed significant increases in only tidal volume (P = 0.01). Ventilatory response to treadmill exercise monitored the oxygen uptake, CO2 elimination (VCO2), minute ventilation (VE), and respiratory exchange ratio at each of four workloads. An analysis of the covariance (ANCOVA) for the slopes revealed no significant variation between test periods. The ANCOVA for the means showed increases in VE and VCO2. These results suggest a stimulatory role for synthetic progestins, although ventilatory performance in response to moderate exercise does not appear compromised.

Adult↗
PubMed1978

Comparative studies on two combination oral contraceptives, one containing synthetic estrogen, the other "natural" estrogens.

Two combined oral contraceptives, one containing ethinyl estradiol and the other micronized estradiol and estriol, were compared by measuring a variety of endocrine and renal parameters over nine months. Significant changes were observed in plasma renin activity (P.R.A.) on the synthetic estrogen. Much larger changes were observed in the total urinary estrogens on patients taking the "natural" estrogens reflecting the amount of estrogens required to be excreted in the urine.

Adult↗
PubMed1981

[Vascular thrombosis in synthetic estrogen-progestogen users: an immune mechanism (author's transl)].

In a number of women the use of combined oral contraceptives (OC) may induce the production of anti-ethinylestradiol antibodies circulating as immune complexes (IC) and which precipitate when the serum is brought at 25% saturation in ammonium sulphate. Testing for tests ICs in 50 women who had never taken OCs, in 100 women on OCs but otherwise healthy, and in 17 women on OCs presenting with vascular thrombosis showed that 20% of all healthy women and more than 95% of women with thrombosis were immunoreactive. The statistically significant correlation found between thrombosis and the presence in the serum of ICs and anti-ethinylestradiol antibodies suggests that an immune mechanism might be responsible for the vascular lesions induced by oral contraceptives containing synthetic estrogens.

Adult↗
PubMed1985

Residual vascular risk of discontinued oral contraception. Role of antibodies to synthetic sex hormones.

Recent epidemiological data indicate that the risk of thromboembolic disease associated with oral contraception (OC) may persist after discontinuation of the drug. It was demonstrated on the other hand that antibodies to sex steroid hormones which develop in OC users, were significantly correlated with the incidence of thrombosis. It is well known that antibodies may persist years after the antigenic stimulation. So it was of interest to see if the eventual occurrence of thrombosis in ex-users might be correlated with the presence of anti-sex steroid antibodies remaining after stopping OC. Thirty-eight women with thrombosis on OC and positive antibody levels, who were required to stop the pill, were followed for periods ranging from 1 to 10 years. No disappearance of anti-ethinyl-estradiol antibodies (anti-EE ab) was observed except for 2 cases. On the other hand, 109 patients with thrombosis either current- (50), past- (29), or never-users (30) of OC were compared to 102 controls of similar groups. Results indicate that the levels of anti-EE ab, and the percentage of women who had anti-EE ab, were similar in those who experienced thrombosis either in the course of OC or after discontinuation. A significant difference was observed between both cases who were current- or ex-users and their controls.

Adult↗
PubMed1989

A comparative study of Norinyl 1/35 versus Lo-Ovral in Ile-Ife Nigeria.

A comparative analysis of those women on Norinyl 1/35 versus those on Lo-Ovral showed those on Norinyl 1/35 were significantly (P less than or equal to 0.05) older than women in the Lo-Ovral group. There were no significant differences (P greater than or equal to 0.05) between the groups for other characteristics at admission. There were no significant differences (P greater than or equal to 0.05) between the groups at follow-up in the number of women reporting serious complications, menstrual complaints or other pill-related problems. The continuation rates at 12 months were 79.4 for the Norinyl 1/35 group and 76.7 for the Lo-Ovral groups. There were no pregnancies reported during the study period.

Adult↗
PubMed2004

[Present and potential uses of mifepristone in gynecology, obstetrics and other medical specialties].

Mifepristone, a derivative of norethindrone, a first generation synthetic progestative, has a very potent antiprogestative activity and to a lesser degree antiandrogenic and antiglucocorticoid activities. This action makes it potentially useful in the treatment of multiple hormone dependent diseases in obstetrics-gynecology as well as in a variety of medical specialties such as neurology, ophthalmology, and oncology. Nevertheless, the label of abortive pill has incited numerous ethical and political debates concerning the permission to market this drug, and this has contributed to the delay in the assessment of the potential indications of mifepristone. Largely under-utilized in practice despite its increasing theoretical benefit, clinical studies should now de conducted. Thus, based on an international review of literature during the last ten years, we have shed light on the present and potential indications of mifepristone in medical practice.

Abortifacient Agents, Steroidal↗
PubMedDate not supplied

Mifepristone (RU 486): current knowledge and future prospects.

Mifepristone (RU 486) has received recent attention for its effects as an abortifacient. Mifepristone has not yet been approved for use in the United States. The Food and Drug Administration issued an "approvable letter" in September 1996, but mifepristone will not be available in the United States until a new manufacturer is found. Experience with mifepristone is extensive in Europe, and there have been retrospective studies and large, controlled clinical trials of its efficacy. It is most efficacious when administered to women who are less than 8 weeks pregnant, in a single 600-mg oral dose followed 48 hours later by administration of intravaginal misoprostol. This regimen has a success rate of 98%, as do most surgical abortive procedures. The most frequent adverse effect is painful contractions, which occur in up to 93% of women, with oral analgesia required in as many as half the cases. Large-scale surveys of women who elected medical abortion reported high patient satisfaction. Mifepristone is likely to have additional clinical uses. Researchers are exploring mifepristone's potential uses in cervical ripening and labor induction; contraception; delivery after intrauterine demise; treatment of breast cancer, unresectable meningioma, and prostate cancer; amelioration of endometriosis; and management of Cushing syndrome.

Abortifacient Agents, Steroidal↗