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PubMed1981

[The effect of norethisterone acetate and 17 alpha-cyanomethyl-estradiol-3-methyl ether on the serum lipid levels].

Noraethisterone acetate in a dosage of 5 mg/day led to a decrease of the triglyceride and beta-lipoprotein level in the blood serum in postclimacteric patients. In females with hypercholesterolamias by 17 alpha-cyanomethyl-oestra-diol-3-methylether a decrease of cholesterol by 12.9% was achieved. The sexualspecific properties of these connections forbid, however, a long-term therapy of hyperlipoproteinaemias.

Aged↗
PubMed1989

Long-term oral contraceptive use does not affect trabecular bone density.

To determine whether long-term exposure to exogenous estrogen in oral contraceptives influences trabecular bone mass in premenopausal women, we studied 25 closely matched, healthy, premenopausal women, who were recruited from an active obstetrics and gynecology practice. Eleven women had never used oral contraceptives, and 14 women had used oral contraceptives for a minimum of 67 months. All oral contraceptive users had used preparations that provided a minimum of 50 micrograms mestranol per day. Trabecular bone density was determined by quantitative single-energy computerized tomography of the L1-3 lumbar vertebral bodies. Trabecular bone density was similar for both the control group and the oral contraceptive users, 160.6 +/- 6.9 versus 161.2 +/- 7.4 mg/ml, respectively. The power to detect a 15% difference in bone density between these two samples was 0.87. We concluded that long-term, premenopausal oral contraceptive use has no effect on vertebral bone density.

Absorptiometry, Photon↗
PubMed1986

Contraceptive steroids increase hepatic uptake of chylomicron remnants in healthy young 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)

Adult↗
PubMed1981

Treatment of advanced breast cancer with progestins.

This paper reviews the theoretical background for the use of progestins in advanced breast cancer and the clinical experience obtained from 13 major studies. The average rate of response is about 30%, with somewhat higher rates when the dominant site of disease is localized to soft tissue and to bones, compared with viscera. Furthermore it seems that cross resistance between progestin therapy and other endocrine therapies is only partial. However, response rates related to previous therapy and to important prognostic variables such as age of the patient, disease-free interval and hormone receptor content of the tumor tissue are poorly elucidated. Only limited data are available concerning response rate in relation to dose and route of administration and data from prospective randomized trials to analyze these relations are still lacking. Considering the only modest side effects of treatment with progestins and the clinical and theoretical evidence favoring a mode of action different from that of other endocrine therapies, progestins are drugs with interesting qualities. Therefore future controlled studies with progestins alone or in combination with other systemic therapies should be carried out to establish the therapeutic efficacy of progestin therapy in primary and advanced disease.

Age Factors↗
PubMed1987

Pharmacokinetics of contraceptive steroids in patients with cystic fibrosis.

The pharmacokinetics of the commonly used contraceptive steroids ethinyloestradiol and levonorgestrel were investigated after oral and intravenous administration in six women with cystic fibrosis. The results were compared with data obtained from healthy women of similar age. The total body clearance of ethinyloestradiol was significantly higher in the patients with cystic fibrosis (0.61 (SD 0.19) l/h/kg) than in control women (0.32 (0.16) l/h/kg; p less than 0.02). In addition, the oral bioavailability of ethinyloestradiol was greater in women with cystic fibrosis than in controls (76.9% (11.7%) compared with 47.3% (7.5%); p less than 0.001). As a result of these two changes, the area under the plasma concentration--time curve after an oral dose of ethinyloestradiol was similar in patients and controls. The pharmacokinetics of levonorgestrel did not differ significantly between patients with cystic fibrosis and healthy women. The data suggest that women with cystic fibrosis will receive similar contraceptive protection from these steroids as do healthy women.

Adult↗
PubMed1983

Pharmacokinetics of levonorgestrel in Indian women.

A low dose combination pill containing levonorgestrel 150 micrograms and ethynylestradiol 50 micrograms was administered orally to 13 women. Based on their anthropometric index they were classed as well-nourished (Group A) or undernourished (Group B). Plasma levels of levonorgestrel at various intervals after dosing were analysed by a specific radioimmunoassay and its pharmacokinetic parameters were computed. Peak plasma levels in both groups occurred within 2 h and the absorption half-lives were also similar. The decline in plasma levonorgestrel showed a tri-exponential decline in all Group A women, whereas it was biphasic in most of Group B. The pi t1/2 was lower in Group A women and the alpha-phase was found to be negligible in Group B. A significant positive correlation between elimination half-life (beta t1/2) and some of the anthropometric indices suggests a possible role of nutritional status in the metabolic handling of levonorgestrel.

Adult↗
PubMed1983

Metabolic effects of two triphasic formulations containing ethinyl estradiol and dl-norgestrel.

The metabolic effects of two triphasic oral contraceptive (OC) preparations containing dl-norgestrel (dlN) and ethinyl estradiol (EE) were studied in young women. The marked difference in the two preparations was in the progestogen content, allowing the study of the metabolic effects of high and low progestogen in oral contraception. The results suggest that high progestogen increases serum sodium, potassium, blood urea nitrogen, creatinine, total protein, albumen, and lactic dehydrogenase. An increase in aspartate transaminase and a decrease in alkaline phosphatase were probably estrogen-related. High progestogen significantly reduced the fasting blood glucose levels (p less than .001). Both preparations significantly increased the levels of cholesterol and triglycerides in women who had not taken OCs for 3 or more months, and with the low progestogen preparation these increases are dissimilar to the effects reported in the triphasic preparations containing levonorgestrel.

Adult↗
PubMed1988

Pharmacokinetic study of levonorgestrel used as a postcoital agent.

The pharmacokinetics and pharmacodynamics of levonorgestrel (LNG) were studied in six women given 0.75 mg LNG orally for seven days during the periovulatory phase of the menstrual cycle. Steady-state concentrations of LNG were reached within three days and serum LNG concentrations at various times on day 7 were generally lower than on day 1, presumably due to a reduced serum level of SHBG. On day 7 the volume of distribution was significantly increased and Co significantly decreased and both the clearance and elimination half-life were higher on day 7 than on day 1. Half-lives varied from 5.6 to 25.1 hours. The day-to-day intra-subject variations in serum LNG concentrations ranged from 23% to 80%. Serum concentrations of pituitary and ovarian hormones suggested that ovulation was not inhibited in four of the six subjects and was delayed in the remaining two. No significant changes in serum prolactin levels were observed.

Absorption↗
PubMed1988

Clearance of levonorgestrel from the circulation following removal of NORPLANT subdermal implants.

The disappearance of levonorgestrel from plasma after the removal of NORPLANT subdermal implants was studied in 12 women who had been treated from 5.5 to 78 months. The existence of one or two half-lives for the rate of disappearance was assessed. The influence of body weight, body fat and length of treatment upon levonorgestrel clearance was studied through stepwise regression analysis. It was found that the levonorgestrel decay rate after implant removal can be entirely accounted assuming one half-life of 42 +/- 16 h (mean +/- SD; range 13 to 62 h). Stepwise regression analysis showed that levonorgestrel half-life is positively correlated with body weight and not significantly correlated with the length of treatment or body fat. It is concluded that, after long-term administration of levonorgestrel via subdermal implants, the major part of the steroid is cleared from plasma within 96 h and that only trace amounts are detected in the following days.

Adult↗
PubMedDate not supplied

3H-thymidine incorporation into mammary carcinoma cells obtained by needle aspiration before and during endocrine therapy.

3H-thymidine autoradiography was used to evaluate DNA-synthesis in carcinoma cells obtained by fine-needle aspiration biopsy from mammary carcinomas. Needle aspirates were analyzed before and after oophorectomy, and before and during treatment with oestrogen or anti-oestrogen (tamoxifen). Tumor regression occurred in 18 patients-in one of four following oophorectomy, in 15 of 38 treated with tamoxifen and in two of three given oestrogen. Seven tumors remained stationary for long periods-up to a year. In 20 cases there was tumor progression. Regression of tumors was preceded by a decrease in the fraction of 3H-thymidine-labeled cells (s-phase cells). The tumors that remained stationary or progressed retained significant levels of 3H-thymidine incorporation. This study thus showed that 3H-thymidine autoradiography can give an early estimate of tumour response to endocrine therapy. Considerable differences were found between the carcinomas in regard to proportions of S-phase cells. Further insight into this parameter may be useful for planning chemotherapy with S-phase specific agents.

Adult↗