Ovulation inhibition by a new low-dose progestagen.
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Pharmacokinetics of norethindrone (NET) was evaluated in eleven women belonging to a low socio-economic group and in five womem belonging to the high socio-economic group after the administration of an oral dose of 0.35 mg NET minipill on an empty stomach. Blood samples were collected at different intervals of time over a period of 24 hours. Plasma NET was estimated by radioimmunoassay. In all women, peak levels of NET occurred within 1-2 hours and a semi-log plot of plasma NET levels showed a biexponential decline. The half-life of plasma NET clearance was relatively shorter in women of low socio-economic group with poor nutritional status as indicated by anthropometric indices, as compared to that in well nourished women of high socio-economic group. There was a significant positive correlation between weight/(height) 2x 100 index on the one hand and t1/2 (beta) on the other in all the women studied, thereby suggesting a role for nutritional status in the metabolic handling of NET.
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In an attempt to elevate the concentration of progestin-binding components in human renal cell carcinoma, 24 patients were treated prior to tumour nephrectomy with various doses of oestrogens, potent inducers of progestin receptor synthesis. Low-dose oestrogen treatment was found to be insufficient to significantly induce progestin-binder synthesis in the tumour tissue. In the carcinoma of patients receiving high-dose oestrogen treatment, the average concentration of R-5020-binding sites did not differ from that of the low-dose group. However, 2 out of these patients (12.5%) exhibited R-5020-binder concentrations in the tumour tissue which exceeded the highest quantities of progestin-binding components found in 88 untreated controls previously analysed in our laboratory.
A trial was carried out in 10 healthy women to study the effects of withdrawal of treatment with 0.5 mg lynestrenol per day, for 3 successive days during the pre-ovulatory phase, on the physiological properties of the cervical mucus, vaginal cytology and pituitary and ovarian functions. In most cases, the amount, Spinnbarkeit and ferning of the cervical mucus and sperm penetration remained the same as that before interruption of treatment. In 2 women, the ferning altered to 'good' for 2 to 3 days as the amount of mucus increased slightly. Spinnbarkeit increased at the same time and sperm penetration was good. The changes in LH and FSH excretion suggested that ovulation possibly took place in 1 of the women studied. A mid-cycle oestrogen peak was seen in 2 women. No side-effects were reported during the study apart from irregular intermenstrual bleeding in 1 woman.
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The localization of the Mg++-activated adenosine triphosphatase (ATPase) in the human Fallopian tube has been studied by means of histochemical methods. The samples were obtained from 18 women in the age from 23--62 years. Some of them were treated by various steroid hormones. Endosalpinx ciliary ATPase-activity represents dynein and is therefore an indicator of ciliary motility. Estrogens and gestagens have a different influence on the ATPase-activity. All cilia of one ciliated cell react in the same manner and may be regarded as a reaction unit. The relation of negative to positive ciliary borders differs characteristically in the tubal isthmus, ampulls and infundibulum and coincides with commonly known phenomena of egg transport through the oviduct. Postovulatory, reaction units increase in ampulla and infundibulum compared with the proliferative phase. The oviducts of postmenopausal women possess but a scanty outfit of reaction units. Short-time treatment with estrogen in the early secretory phase results in a great number of reaction units in all tubal segments; a similar treatment in the proliferative phase diminishes the reaction units in the ampulla. Midcycle progesterone treatment activates the ciliary ATPase in the isthmus. Low doses of lynestrenol (minipill) in the proliferative phase leads to a decrease of reaction units in all tubal segments; the pattern of ciliary reaction under low doses of lynestrenol at the time of ovulation coincides with that of the proliferative phase. Treatment with a contraceptive steroid (0,05 mg ethinylestradiol and 0,25 d-norgestrel) causes a considerable activation of the ciliary ATPase in all portions of the oviduct.
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A study was performed to further evaluate pituitary-ovarian function in women receiving an oral contraceptive preparation. Basal hormone levels (follicle stimulating hormone, luteinizing hormone, estradiol and prolactin) and gonadotropic response to gonadotropic releasing hormone were studied in 12 healthy, regularly ovulating women in the early follicular and mid-luteal phases of their menstrual cycle (non-treatment control period). These same women were then given NORDETTE (ethinyl estradiol 30 microgram +d-Norgestrel 150 microgram) cyclically for 3 months. In the third month of treatment, the tests were repeated on day 21, i.e. after 21 active pills, and on day 28, i.e. after 21 active and 7 inactive tablets. On active preparation, basal luteinizing hormone, follicle stimulating hormone and estradiol and gonadotropin response to gonadotropin releasing hormone were significantly suppressed. However, by day 28 (after completion of the inactive tablets), basal gonadotropin and estradiol concentrations and the gonadotropic response to gonadotropic releasing hormone were not significantly different to their pretreatment levels. No consistent change in prolactin concentration occurred as a result of oral contraceptive therapy. These results indicate that the 'active' component of even a relatively low-dose pill causes considerable suppression of pituitary-ovarian function but that after 7 days of placebo, pituitary function and basal estradiol secretion have virtually returned to normal.
This was a multicentre general practitioner study using a new low dose oral contraceptive, Ovamin 30 (ethinyloestradiol 30 microgram, ethynodiol diacetate 2 mg). Results showed a pregnancy rate calculated as a Pearl Index of 0.4. An analysis of bleeding patterns showed consistently acceptable cycle control. From these results it would appear that Ovamin 30 is an effective and well tolerated low dose oral contraceptive preparation.
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