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In discussing the possible vascular complications of oral contraception, one must differentiate between venous and arterial effects. Different estrogen-progestogen combinations have different effects on the hemostatic system.
Both estrogens and progestogens modify carbohydrate metabolism, and their ultimate effect depends upon the ratio of one to the other. The effect of progestogens themselves, which are responsible for increased insulin secretion and for insulin resistance, varies according to their androgenicity but increases according to the series pregnane, estrane and gonane. In contrast, estrogens impair the initial secretion of insulin by the pancreas. The prolonged use of combined oral contraceptives containing the powerful progestogen levonorgestrel is associated with mild but continuing glucose intolerance and with marked insulin resistance.
A study was made of the content of estrogen and progesterone receptors (ER and PR, respectively) in the cytosol and nuclei of the decidual tissue of women in induced and spontaneous abortion at 7-12 week pregnancy. Abortion was done surgically (control group) and in preliminary cervical dilatation with the help of intravaginal suppositories with a synthetic prostaglandin analog of E1-16.16-dimethyltrans-delta 2-PGE1 (ONO-802) group or laminaria. The level of ER in the cytosol and nuclei of the decidual tissue of the control group was twice as low as that of PR, and the ER/PR ratio in cell fractions as well as in general cell receptors was 0.58 +/- 0.09, 0.42 +/- 0.07 and 0.56 +/- 0.07, respectively. The suppositories with ONO-802 caused a statistically significant decrease in the PR content in each of the cell fractions and cytoplasmic ER resulting in an increase in the ER/PR ratio to 0.87 +/- 0.06 (P less than 0.05) in the cytosol, 0.09 +/- 0.24 (P less than 0.05) in the nuclei, and 0.86 +/- 0.8 (P less than 0.05) in the total cell. A decrease in the PR level in both cell fractions and the ER level in the fraction of the nuclei with an acute increase in the content of cytoplasmic ER was marked in spontaneous abortion. The ER/PR ratio also rose to ER and was 1.98 +/- +/- 0.2 (P less than 0.001) in the cytosol and 1.02 +/- 0.16 (P less than 0.05) in the total cell. It was concluded that an absolute and/or relative decrease in the PR level plays an important role in mechanism of abortion.
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In patients with hypogonadism, the exact cause of the deficient androgenisation is not always clinically apparent. The data presented demonstrate that by means of hormone measurements, basally or after stimulation tests, the exact level of the lesion can usually be determined. This allows a decision with regard to appropriate therapy to be made on the basis of an accurate diagnosis. In many instances basal measurements of pituitary and gonadal hormones are all that is required to decide the level of the lesion. Care in interpreting basal levels is required, however, in view of methodological limitations and of known physiological variations with age, time of day and hour-to-hour fluctuations. If the basal hormone levels are borderline, or if the 'reserve function' of part or all of the hypothalamic-pituitary-gonadal axis needs to be assessed, than the appropriate stimulation test should be performed. The indication for these stimulation procedures and results obtained in different conditions are described and problems of interpretation discussed.
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In a double-blind clinical study, 93 patients with vulvovaginal candidiasis were randomly assigned to treatment with either clotrimazole (1%) or miconazole (2%) vaginal cream for seven days. The treatments were comparable in reducing the severity of presenting signs and symptoms. At one and four weeks posttherapy, negative vaginal cultures were found in 84.4% and 75.0%, respectively, of the clotrimazole-treated patients and in 85.4% and 74.5%, respectively, of the miconazole-treated patients. The incidences of recurrence/reinfection and treatment failures were comparable in the two groups. Treatment failures and recurrences/reinfections were not correlated with positive perianal cultures for Candida species. Patients using oral contraceptives had a higher incidence of positive vaginal cultures at four weeks posttherapy than did patients not using oral contraceptives or using other methods.
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Histidine-rich glycoprotein (HRG), a 3.8 S-alpha 2-glycoprotein recently identified as a new fibrinolysis regulating protein, was determined by an electroimmunoassay in samples of plasma collected during one menstrual or hormone cycle in 15 young women and in 11 women using oral contraceptives with 30 micrograms ethinyl oestradiol and 150 micrograms levo-norgestrel. Distinct individual levels caused the within-group variations of plasma HRG to be larger than the individual variations. In the hormone group the plasma HRG levels were decreased to about 75% of the normal, while the fluctuations during the cycle were minor in both groups.
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The inhibitory effect of five ionophores, namely, A23187, nonactin, nigericin, monensin and m-chlorocarbonyl cyanide phenylhydrazone, on human sperm motility were measured with a trans-membrane migration method. The concentrations of A23187 and nigericin that decreased sperm motility to 50% of control were 20 microM (10.5 mg/l) and 8 microM (5.8 mg/l), respectively. Because these two ionophores were more potent than previously reported membrane-active sperm-immobilizing agents, we propose that ionophores could be a new category of vaginal contraceptive if a pharmaceutical preparation that is safe to be administered in vivo can be developed.
To assess the effect of hormonal monthly injectable contraceptives upon the serum values of immunoreactive prolactin (Prl), three groups of women of reproductive age exposed to different estrogen-progestogen injectable formulation for a minimum of one year were studied. The first group (n = 10) received dihydroxyprogesterone acetophenide 150 mg and estradiol enanthate 10 mg (DHPA/E2-EN), Group 2 (n = 21) received medroxyprogesterone acetate 25 mg and estradiol cypionate 5 mg (MPA/E2-C) and Group 3 (n = 19) was exposed to norethisterone enanthate 50 mg and estradiol valerate 5 mg (NET-EN/E2-V). A group of IUD users (n = 16) served as the control group. Serum Prl and 17 beta-estradiol (E2) concentration were determined in blood samples (0 and 15 min.) on days 0 (day of last injection), 10, 20 and 30 after last contraceptive injection. The results demonstrated a slight though not significant increase (p greater than 0.05) in serum Prl in the three experimental groups as compared with the IUD control group. This increase in Prl levels observed on day 10 post-last injection never exceeded the upper limits of the normal range (20 ng/ml). Overall, the data demonstrated that the chronic administration of these estrogen/progestogen once-a-month injectable contraceptives does not affect the Prl baseline secretion in women.
The magnitude and duration of elevated plasma progesterone levels resulting from subdermal implantation of progesterone pellets were investigated in full nursing women. This condition was chosen because it is associated with a low rate of ovulation and minimal endogenous progesterone production. In addition, treatment with progesterone pellets was intended to be a substitute for oral or parenteral administration of synthetic progestogens to nursing mothers. A control group of full nursing women receiving no hormones provided blood samples so that basal plasma progesterone levels from the second to the sixth post-partum month could be assessed. Progesterone pellets were implanted subdermally on day 30-35 after delivery. Insertion of 2, 4 or 6 pellets each containing 100 mg of progesterone caused an initial elevation of plasma progesterone to 5.9, 9.9 and 13.5 nmol/l, respectively. This initial elevation was followed by a gradual decline, so that basal levels were attained at 70, 100 and 150 days after insertion of 2, 4 or 6 pellets. Implantation of 6 progesterone pellets led to a significant decrease in the ovulation rate of nursing women. These results indicate that subdermal implantation of 6 progesterone pellets can provide biologically effective levels of the hormone for up to 5 months.
The site of gonadotrophin inhibition in long-term users of injectable contraceptives is still debatable. The pituitary response to LHRH (50 micrograms, I.V.) was assessed in 32 women. Sixteen cases were using either medroxyprogesterone acetate (DMPA; n = 8 150 mg I.M. every three months) or norethisterone enanthate (NET-EN; n = 8, 200 mg every 2 months) for at least 18 months. The remaining cases (n = 16) were normal fertile females not using any hormonal contraceptive (control group). The pituitary response to LHRH injection in both injectable subgroups was nearly identical to that in the control group. Neither the basal levels nor the net increase in gonadotrophins following LHRH injection were significantly different in the study groups from those of the control group. Long-term use of DMPA or NET-EN does not affect the pituitary responsiveness to LHRH injection and the pituitary is not a primary site for ovulation inhibition in these cases.
In this paper we report on changes of the Ag-stained NOR (Ag-NOR) and Ag-stained acrocentric association (Ag-AA) frequencies in lymphocytes of women with polycystic ovaries, galactorrhea, or taking oral contraceptives. The results showed that Ag-AA frequencies were increased significantly in all three study groups while the Ag-NOR frequencies apparently did not increase. We assume that a difference in average Ag-NOR frequency between the two groups may be a measure of the change in the number of active rRNA genes, and that differences of Ag-AA frequency among populations reflect the change in transcriptional rate of the active rRNA genes.
Pharmacokinetics and pharmacodynamics of a long-acting injectable microcapsule, poly(DL-lactide-co-glycolide), delivery system were tested in 10 women. Two doses (75 or 100 mg of norethindrone) were administered by intramuscular injection. Treatment suppressed ovarian function and inhibited ovulation for 3 months in all subjects. Levels of norethindrone in subjects who received the 100 mg dose were proportionately higher than those in subjects who received the 75 mg dose. Subsequent to the injection, there was a rapid rise in the serum levels of norethindrone followed by a gradual decline until 8 to 10 weeks. Between 10 and 20 weeks after treatment, there was a secondary rise and fall in the serum levels of norethindrone. Treatment caused suppression of the endometrium for 3 months, and, except for spotting and irregular menstrual cycles, there were no adverse side effects. Treatment had no significant effect on serum lipids.