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[Change in the RNA content in the rat endometrium under the action of estrogen-megestrol and neurotropic substances].

The effect of the hormone-like estrogen-progestagen preparation megestranol and of megestranol-spasmolytin combination on the activity of metabolic processes in the uterine mucous membrane was studied in experiments on rats. Results of cytochemical studies showed megestranol and megestranol-spasmolytin combination to change the metabolic activity of the uterine mucous membrane resulting in a decrease in the RNA content in the epithelial cells of the endometrial glands, thereby creating conditions preventing normal implantation and development of the fertilized ovum.

Animals

Oral contraception.

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Contraceptives, Oral

[The effect of low dose gestagens on the hypothalamic-pituitary-ovarian axis].

The contraceptive effect of continuous treatment with low dose progestogens (minipill) has been attributed mainly to alterations of the cervical mucus and the endometrium. This study was undertaken to investigate the effect of low dose progestogens on hypothalamic-pituitary-ovarian function. Plasma concentrations of follicle stimulating hormone (FSH), luteininzing hormone (LH), estradiol-17 beta (E-2) and Progesterone were measured daily during apparently ovulatory menstrual cycles and during treatment cycles with different low dose progestogens. From the results obtained it was concluded that the minipill has a clear-cut effect on the LH/FSH peak at midcycle and on corpus luteum function. A cyclic secretion of E-2 is maintained in the majority of cases. In a few treatment cycles however, follicular maturation was suppressed as indicated by low E-2 concentrations. It was concluded that the minipill exerts a profound effect at the central and ovarian level which contributes to its satisfactory contraceptive efficacy.

Adult

High-dose medroxyprogesterone acetate (MPA) treatment in advanced breast cancer. A review.

Medroxyprogesterone acetate (MPA) when employed at high doses (greater than or equal to 500 greater than or equal to 1000 mg/day i.m.) can produce objective remission with improved survival in about 30% of postmenopausal women with advanced breast cancer resistant to cytotoxic drugs and endocrine therapies. When administered to women not previously treated with chemotherapy, the objective remission response rate reached 40%. From available evidence, high dose MPA can be considered a useful agent in the treatment of advanced breast cancer in postmenopausal women with soft tissue, pulmonary, pleural or osseous involvement even when patients have become refractory to prior hormone and cytotoxic therapies. Early results suggest that the response rate can be increased in patients with estrogen and/or progesterone-positive receptors. It is note worthy that in a study conducted on postmenopausal women resistant to cytotoxic and/or hormonal drugs, the median duration of survival was 13.5 months, while CRs plus PRs did not reach the median at 24 months after starting MPA treatment. High dose MPA is essentially devoid of major side effects. Relief of pain, increase in appetite and body weight, and sense of well being are characteristic features of the improved quality of life under MPA treatment. However, a gluteal abscess (from 2% to 20% dose related) is the most frequent side effect. A promising area for future studies is combined therapy using hormonal and cytotoxic agents or alternating sequential combinations. Well-designed studies are needed to develop means for increasing the complete response rate and therefore survival. Recent studies of combined chemo- and hormonal (MPA) therapy have yielded objective tumor regressions of 53 to 80% with an increased rate of complete remissions and duration of response.

Animals

Pharmacological studies of a contraceptive drug anordrin.

A new oral contraceptive--Anordrin has been discovered. It is an A-Nor-steroid with some estrogenic activity and possessing a significant anti-fertility activity in mice, rats, rabbits, hamsters and dogs. In rats, AF-53, administrated repeatedly, led to sterility but did not alter mating behaviour, and the fertility of the animals recovered soon after cessation of the medication. In sub-minimal antifertility doses it has no teratogenic effect. Acute and chronic toxicity tests in animals showed that this drug did not cause any apparent abnormality in the blood picture, liver and renal functions, as well as in the histological examinations of organs. Experiments with 14C-labelled Anordrin showed that this drug could be absorbed rapidly but not completely in the gastrointestinal tract. The peak blood level was usually attained at 9 hours after administration. The drug excreted in the urine reached a maximum in 10--12 hours. Higher radio-activity was found in bile and gastrointestinal tract and was also excreted in large amounts in the feces. In clinical trials it is administrated only once post-coitally. The time for taking the drug is not limited by the menstrual cycle and it is unnecessary to be taken successively. Thus Anordrin is a convenient, safe and effective oral contraceptive drug.

Alkynes

Subdermal norethindrone pellets -- a method for contraception?

The mode of action of compressed pellets containing 85 per cent norethindrone (NET) and 15 per cent cholesterol was studied. Four pellets were inserted subcutaneously, in each of five healthy volunteers and left in place for 200--229 days. The NET content of the pellets varied between 23.9 mg and 25.6 mg; and the cholesterol content between 4.2 mg and 4.5 mg. Plasma levels of NET, estradiol and progesterone were determined by radioimmunoassays. Plasma levels of NET varied mostly between 1--2 ng/ml the first month after insertion. After two months plasma levels of NET ranged between 0.5 ng/ml and 1 ng/ml in all volunteers and there was a gradual decrease of the plasma NET levels throughout treatment. Pronounced day-to-day variations in plasma NET levels were recorded. The release rates of NET was calculated to be between 187 micrograms/day and 243 micrograms/day among the five volunteers. Ovulations occurred in four out of five subjects during treatment. This study indicates that the release of gestagen from four NET pellets was only initially high enough to completely inhibit ovulation and that to accomplish full contraceptive efficacy, a higher dose, i.e. more pellets, would have to be inserted.

Adult