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At least 1,135 records · Page 63Linked to original sources
PubMed1990

Pharmacokinetics of oestrogens and progestogens.

There are large inter- and intra-individual variations in the serum concentrations of natural and synthetic sex steroids irrespective of the route of administration. Oral ingestion of steroids has a stronger effect on hepatic metabolism than parenteral administration, as the local concentration in liver sinusoids are 4-5 times higher during the first liver passage. Oestradiol and oestrone are interconvertible, dependent on the local concentrations in liver and target organs, and oestrone sulphate serves as a large reservoir. The oestrone/oestradiol ratio has no physiological significance, as oestrone is only a weak oestrogen. Oestrone is both a precursor and a metabolite of oestradiol. Oestriol is extensively conjugated after oral administration. Therefore, the oestriol serum levels are similar after oral intake of 10 mg and after vaginal application of 0.5 mg oestriol resulting in similar systemic effectiveness. Conjugated oestrogens can easily enter the hepatocytes but are hormonally active only after hydrolyzation into the parent steroids. Ethinylestradiol which exerts strong effects on hepatic metabolism and inhibits metabolizing enzymes, should not be used for hormone replacement therapy. Among the progestogens, the progesterone derivatives have less effects on liver metabolism than the norethisterone derivatives (13-methyl-gonanes and 13-ethyl-gonanes). The highly potent 13-ethyl-gonanes are effective at very low doses, because of a slow inactivation and elimination rate due to the ethinyl group.

Estrogens↗
PubMed1987

The antiprogesterone steroid RU 486: a short pharmacological and clinical review, with emphasis on the interruption of pregnancy.

In this review we have briefly outlined the clinical applications and mechanism of action of the progesterone antagonist RU 486. RU 486 has been successfully used in a variety of conditions to regulate the reproductive cycle and to control fertility in women. We suggest that the mechanism by which RU 486 acts during the cycle and early pregnancy is probably by affecting mainly the endometrium. During late pregnancy, the compound has significant effects on the myometrium including the induction of gap junctions between myometrium cells, which is required for muscle contractility during labour. The use of RU 486 has helped to demonstrate that progesterone is required for maintenance of the late stages of pregnancy in women.

Abortion, Induced↗
PubMed1992

Influence of menstrual cycle, parity and oral contraceptive use on steroid hormone receptors in normal breast.

Steroid receptor was assessed immunohistochemically in 158 samples of normal breast for variation through the menstrual cycle. Patterns and intensity of reaction were used in a semi-quantitative scoring system to examine the influence of cycle phase, cycle type, parity and age. The changes in oestrogen receptor for natural cycle and oral contraceptive (OC) cycles indicated down-regulation by progestins. Progesterone receptor did not vary significantly in natural cycles, but increased steadily through OC cycles. This study provides strong evidence that both oestrogen and progesterone influence breast epithelium, but dissimilarities from the endometrium are apparent. The interval since pregnancy had a significant negative effect on frequency and score of oestrogen receptor and score of progesterone receptor. Multivariate analysis established the phase of cycle and OC use as independent significant influences on oestrogen receptor. The interval since pregnancy was an independent significant factor for both oestrogen and progesterone receptor presence.

Age Factors↗
PubMed1985

Pharmacodynamic studies on desogestrel administered alone and in combination with ethinylestradiol.

Most progestogens in oral contraceptives are testosterone derivatives and have androgenic side effects such as weight increase, acne and hirsutism. They pose a problem to many women just like the clinical picture of the polycystic ovary syndrome (PCO) with obesity, hirsutism, acne and amenorrhea. The aim of this study was to evaluate androgenicity of the most used progestogens with special reference to desogestrel which is a new progestogen. Radioimmunoassay was used for hormone determination while serum proteins were determined with electroimmunoassay or in some studies for sex hormone binding globulin (SHBG) with capacity assays. Serum lipids and lipoproteins were determined in serum and after ultracentrifugation in HDL, LDL and VLDL fractions. In a comparative study on levonorgestrel/ethinylestradiol (EE) (n = 10) versus desogestrel/ethinylestradiol (n = 10) the latter combination gave increases in SHBG capacity while the former did not. Similar increases in estrogen-sensitive proteins cortisol binding globulin (CBG) and ceruloplasmin indicated that the estrogenicity and "antiestrogenicity" was the same for the two combinations whereas the androgenicity of levonorgestrel was greater giving a reduction in the EE-induced increase in SHBG (SHBG is increased by estrogens and suppressed by androgens). When giving desogestrel 0.125-0.500 mg and lynestrenol 5 mg alone in daily doses to a group of regularly menstruating women (n = 8) strong suppression of SHBG was achieved while ceruloplasmin, CBG and thyroxine binding globulin (TBG) did not change. TBG is decreased and prealbumin increased by androgenic/anabolic activity but only a moderate increase in prealbumin was found during lynestrenol treatment. The changes in SHBG are probably the result of a dose-dependent receptor interaction related to 17 alpha-alkylation in 19-norsteroids. Twenty women with PCO were treated for 8 months with 0.150 mg desogestrel/0.030 mg EE. Evaluation was done before treatment and after 3 and 8 "pill" cycles regarding androgens, estradiol, SHBG, hirsutism and body weight. Spontaneous menstrual cycles were assessed after treatment. Serum lipids and lipoproteins were studied before treatment and at the end of the third "cycle". In PCO the suppression of increased total and free testosterone levels (in comparison to 22 healthy women) was evident during treatment, concordant with increases in SHBG capacity. Hirsutism was suppressed and body weight was reduced in obese women.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1976

Response to medroxyprogesterone acetate (NSC-26386) as secondary hormone therapy for metastatic breast cancer in postmenopausal women.

We have treated 40 postmenopausal women with documented metastatic breast cancer with medroxyprogesterone acetate. The average age was 63 years and the patients were, on the average, 14 years' postmenopausal. Only two patients had received no prior additive hormone therapy. The remainder had previously received estrogen, androgens, or both. Only two patients had objective evidence of tumor regression. In one patient a metastatic node disappeared for 7+ months, and the other patient had well-documented clinical improvement and control of brain mestastases for 22 months. Two other patients had mixed responses of chest wall metastases (regression of some but not all lesions), lasting 3 and 4 months respectively. Five other patients had obvious subjective benefit. There were four objective responses (10%) and five subjective responses (12%). There was no correlation between route of administration and response. All patients receiving benefit had previously responded to other hormones. Side effects were usually absent or consisted of mild fluid retention; however, four patients had disease stimulation from therapy.

Administration, Oral↗
PubMed1990

Interference with ovulation by sequential treatment with the antiprogesterone RU486 and synthetic progestin.

Seven healthy women were treated with the antiprogesterone RU486, 25 mg/d, on days 1 to 14 of the follicular phase of the menstrual cycle, followed by the synthetic progestin NET in the luteal phase of the cycle. Venous blood samples were collected twice per week. Serum E2, P, and RU486 concentrations were determined by RIAs, and FSH and LH by immunofluorometric assays. Ultrasonography was used to measure the sizes of the follicles. Serum concentrations of FSH and LH were not suppressed during the treatment. Ovulation was apparently suppressed during RU486 treatment according to E2 and P concentrations and ultrasonography findings. During NET treatment, some evidence of ovulation and follicle growth were found during the first treatment periods. During the third treatment cycle, there was no evidence of ovulation (n = 2). Estradiol concentrations were sufficient to stimulate normal proliferative growth of the endometrium during the treatment. Control of bleeding was good. The exact mechanism of action of RU486 on steroid synthesis and ovulation is not clear, but it appears to act at the ovarian level. The evidence indicates that sequential RU486/progestin treatment could be developed to result in suppression of follicular growth and ovulation.

Adult↗
PubMed1993

Contraceptive choices in women with coagulation disorders.

When compared with older reports on the thromboembolic effects of high-dose oral contraceptives, new studies with low-dose oral contraceptives have a significantly reduced risk of thromboembolism. In the absence of risk factors such as smoking or inherited disorders predisposing to thrombosis, the modern low-dose oral contraceptive (< 50 micrograms of estrogen) is a safe and effective choice for contraception in women without symptoms who have family histories of sporadic thromboembolism. An intrauterine device or some form of barrier method is recommended for women who have a personal history of venous thrombus disease. The low-dose oral contraceptive may be a good choice in women taking oral anticoagulants because of the risk of teratogenic effects of anticoagulants and the risks of intraperitoneal bleeding associated with ovulation. In addition, oral contraceptives help diminish the excessive menstrual bleeding often seen in these women.

Blood Coagulation Disorders↗
PubMed1983

Breast cancer in young women and use of oral contraceptives: possible modifying effect of formulation and age at use.

A case-control study of 314 breast cancer patients aged less than 37 at diagnosis and 314 individually matched controls was done to assess the influence of oral-contraceptive (OC) use on the risk of the disease. Long-term use before age 25 of combination-type OCs with a "high" content of the progestogen component was associated with increased risk of breast cancer: the relative risk was approximately 4 after 5 years of such use, and 9 cases and no controls had used such combination-type OCs for more than 6 years before age 25. Use of combination-type OCs with a "low" progestogen component appears to increase breast-cancer risk little or not at all.

Adult↗
PubMed1998

Effects of oral contraceptives containing different progestogens on sodium-lithium countertransport in normal females.

In view of the lack of unanimity on the effect of long-term intake of combined oral contraceptives (OC) on external sodium-dependent lithium efflux, otherwise known as sodium-lithium countertransport (SLC), we undertook a double-blind study to investigate the possible interaction between SLC and OC in healthy women with regular menstrual cycles. In a group of 17 volunteers, aged 27.0 +/- 1.1 years (mean +/- s.e.m.) and weighing 61.4 +/- 2.0 kg, ingestion of 30 microg ethinyloestradiol + 150 microg desogestrel for 3 months caused an increase in SLC activity from a baseline value of 0.254 +/- 0.017 mmol/lcell x h to 0.274 +/- 0.017 mmol/lcell x h (P = 0.05). The activity of the transport system after 6 months treatment remained higher than at baseline (0.280 +/- 0.016 mmol/lcell x h, P < 0.025) but was comparable to that at 3 months. Blood pressure and weight remained unaltered during the study period. In a comparable group of 16 volunteers of age 26.1 +/- 1.3 years and weight 63.5 +/- 2.1 kg, control SLC activity (0.218 +/- 0.012 mmol/lcell x h) was comparable to that after 3 months (0.215 +/- 0.011 mmol/lcell x h) and 6 months (0.216 +/- 0.011 mmol/lcell x h) intake of 35 microg ethinyloestradiol + 2 mg cyproterone acetate. Body weight and blood pressure remained similarly unchanged. These results not only confirm that long-term intake of OC may cause increased SLC activity, but also suggest that the type of the progesterone in the medication used could be an important determinant of such interaction.

Adolescent↗