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Biomedical subjects

B M Landgren

Publications and source records attributed to B M Landgren.

At least 109 records · Page 6Linked to original sources

Studies on ovarian and adrenal steroids at different phases of the menstrual cycle: II. A comparative assessment of the circadian variation in steroid and lutropin levels during the follicular, periovulatory and luteal phases.

In six normally menstruating women, ovarian and adrenal steroids and biologically active lutropin (LH) were measured in peripheral plasma samples collected every 3 h. during a period of 39 h. in the early follicular phase, periovulatory period or luteal phase of three consecutive cycles. The purpose of the study was to assess the influence of the phases of the cycle on the diurnal variation in the levels of different steroids and lutropin following the elimination of the between subject variation. Cortisol, 17-hydroxypregnenolone, dehydroepiandrosterone and androstenedione showed a marked circadian rhythm in all three phases of the cycle. No changes in the levels of cortisol, 17-hydroxypregnenolone and dehydroepiandrosterone with the phase of the cycle were observed when the "morning" samples were considered; however, when the "evening" samples were analyzed, the levels of these steroids were higher in the luteal phase than in the follicular phase. As a result of this increase, the amplitude of the circadian rhythm of these steroids considerably decreased in the luteal phase. The "morning" as well as the "evening" increase observed in the levels of androstenedione during the periovulatory period was not able to mask the circadian rhythm. A circadian rhythm in pregnenolone, 17-hydroxyprogesterone, testosterone, and dihydrotestosterone levels was detected only in certain phases of the cycle. All these steroids showed a circadian rhythm in the early follicular phase. The rhythm of pregnenolone and 17-hydroxyprogesterone was still present in the periovulatory period but was no longer detectable in the luteal phase, meanwhile that of testosterone and dihydrotestosterone was not demonstrable neither in the periovulatory period nor in the luteal phase. Compared to the levels of the follicular phase, an increase in pregnenolone and 17-hydroxyprogesterone levels was observed in the periovulatory period which was followed by a further rise in the luteal phase. This increase completely masked the circadian rhythm in the luteal phase. An inverse circadian rhythm in lutropin levels was detected during the luteal phase. The "morning" values were lower than those found during the "evening" period. No such changes were observed in the other phases of the cycle. In none of the phases studied did the levels of progesterone or estradiol show any circadian variation. The data indicate that a circadian rhythm in the peripheral levels of a given steroid mainly depends on the relative contributions of the ovaries and adrenals and that these contributions exhibit major differences at the various phases of the cycles. It is concluded that - in contradistinction to the situation in the human male - in normally menstruating women, the peripheral levels of steroids of predominantly gonadal origin do not exhibit a circadian rhythmicity.

Adrenal Glands↗

Studies on ovarian and adrenal studies at different phases of the menstrual cycle. IV. The effect of dexamethasone suppression and subsequent ACTH stimulation at different phases of the menstrual cycle and following the administration of 150 mg of depot-medroxy-progesterone acetate (DMPA).

In an attempt to assess the effect of depot-medroxyprogesterone acetate (DMPA) on adrenal function, to peripheral levels of a variety of steroids were estimated after dexamethasone suppression and subsequent ACTH stimulation in 5 subjects. The steroid responses observed 16 and 54 days after a single injection of 150 mg of DMPA were compared with those obtained in the same women before DMPA treatment or with those found at different phases of the cycle in another group of 6 normally menstruating women. The levels of cortisol, pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, androstenedione and dihydrotestosterone were significantly suppressed by dexamethasone and stimulated by ACTH in all phases of the cycle, and before and after DMPA administration. The extent of suppression or stimulation (expressed as a percentage) was different in case of different steroids, but was rather constant with regard to the same steroid. Hence, the functional capacity of the adrenal as reflected by the levels of these steroids. Dexamethasone administration did not exert any influence on the levels of progesterone and 17-hydroxyprogesterone during the different phases of the cycle; however, ACTH administration increased the levels of these two steroids in the follicular phase and also after DMPA treatment. The levels of estradiol and lutropin were not influenced by dexamethasone or ACTH at any of the occasions studied. It is concluded that the functional capacity of the adrenal cortex is constant during the various cycle phases and is not affected by the administration of a single dose of 150 mg of DMPA.

17-alpha-Hydroxypregnenolone↗

Pharmacokinetics of ethynyloestradiol in women for different populations.

The pharmacokinetics of a dose of 50 microgram ethynyloestradiol administered orally was studied in fourteen centres. Absorption was rapid and the highest serum concentrations of total ethynyloestradiol were found in most subjects at 1 h and by 24 h concentrations were less than 250 pg/ml. Calculation of the half-lives for absorption, distribution and elimination showed wide variations between subjects, the half-life of elimination varying from 2.5 h to more than 30 h. Bioavailability as measured by the area under the serum ethynyloestradiol concentration-time curve also showed more than a ten-fold variation. Intra-centre differences in the various parameters measured were as large as the inter-centre differences.

Biological Availability↗

Studies on ovarian and adrenal steroids at different phases of the menstrual cycle. III. Steroid and lutropin levels before and after the administration of a single contraceptive dose of depot-medroxyprogesterone acetate (DMPA).

Ovarian and adrenal steroids and biologically active lutropin were measured in peripheral plasma samples obtained from 5 normally menstruating women. Plasma samples were collected every 3 h for a period of 39 hours in the periovulatory period of a pretreatment (control) cycle and then 16 and 54 days after a single i.m. injection of 150 mg of depot-medroxyprogesterone acetate (DMPA). Sixteen days after DMA administration, the levels of estradiol, progesterone, 17-hydroxyprogesterone, and lutropin were reduced to early follicular phase levels. No further decrease was found in 17-hydroxyprogesterone and lutropin levels; however an additional decrease occurred in the levels of estradiol and in the "morning" levels of progesterone 54 days after the administration of DMPA. Furthermore, the levels of pregnenolone, androstenedione, testosterone and dihydrotestosterone were significantly diminished in all samples collected after the administration of DMPA. Fifty-four days following the administration of DMPA, the levels of cortisol and 17-hydroxypregnenolone were significantly reduced. The administration of DMPA did not interfere with the circadian rhythm of cortisol, pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, 17-hydroxyprogesterone, and androstenedione levels. A significant circadian rhythm was also found in testosterone (after 16 days) and lutropin (after 54 days) levels. No circadian variation was found in estradiol, progesterone and dihydrotestosterone levels.

Adrenal Glands↗

Studies on ovarian and adrenal steroids at different phases of the menstrual cycle. 1. Dynamic changes during the periovulatory period.

In order to assess the periovulatory interrelationships between the plasma levels of estradiol, estrone, 17-hydroxyprogesterone, progesterone, cortisol and biologically active lutropin (LH), peripheral blood samples withdrawn from 12 normally menstruating women at 07.00, 15.00 and 23.00 h. during seven days of the midcycle period were analyzed. The estradiol peak varied between 0.86 and 1.50 nmol/l; it preceded the LH peak in 11 subjects and occurred simultaneously with it in 1 case. Although the peak levels of estradiol were significantly higher than those associated with the LH peak, there was no significant difference between the estradiol levels at the LH peak and those found during the 32-hour period prior to the LH peak. Calculation of the estradiol to estrone ratios revealed the existence of two groups of subjects with significantly different ratios. In one group the estradiol levels were significantly lower and those of estrone significantly higher than in the other group. No difference was found between these two groups concerning the other hormonal indices measured. No significant variation was found in the estradiol, estrone and LH levels during the day; however, there was a significant overnight increase in their levels during 3 to 4 days preceding the day of the LH peak. A significant rise in 17-hydroxyprogesterone levels occurred 8 h. before the earliest rise in LH and progesterone levels; on the other hand, in none of the subjects did the first rise in progesterone levels precede the first significant elevation of LH levels.

Adrenal Glands↗

A comparison of the pharmacokinetic properties of three estradiol esters.

In order to assess the pharmacokinetics properties of estradiol cypionate, valerate and benzoate, the daily plasma levels of estradiol and estrone were analysed in groups of 10, 9 and 10 subjects, respectively, before and during 3 weeks after the intramuscular administration of a single dose of 5.0 mg in 1.0 ml arachis oil. In order to minimize the contribution of endogenous estrogens to the plasma levels, all subjects were receiving a combined oral contraceptive consisting of levonorgestrel (150 micrograms) and ethinyl estradiol (30 micrograms) for three months prior to the study and during the study period. The administration of estradiol cypionate gave significantly lower peak levels of estradiol and estrone than that of the valerate and benzoate. Peak plasma levels of estradiol and estrone were reached in approximately 4 days following the administration of estradiol cypionate and in a significantly shorter time (approximately 2 days) following the administration of both the valerate and benzoate. One hour after the injection of the esters, the average percentage increases in plasma estradiol and estrone levels were significantly higher in the valerate and benzoate groups compared to the subjects receiving estradiol cypionate. The average duration of elevated estrogen levels was shortest in the benzoate group (4-5 days) followed by the valerate (7-8 days) and cypionate (approximately 11 days). In none of the subjects studied were elevated estradiol and/or estrone levels encountered 2 weeks after the injection of the various esters. The data suggests that among the three esters studied, the valerate provides the most predictable pharmacokinetic behaviour.

Adult↗

Clinical effects of orally administered extracts of Montanoa tomentosa in early human pregnancy.

Freshly prepared aqueous decocts of the Mexican plant Montanoa tomentosa (Zoapatle) were administered orally to six women in the early stages of pregnancy for two days prior to the interruption of gestation by vacuum aspiration. The daily dose administered varied between 1.0 and 1.4 gm-equivalent of dry leaves per kilogram of body weight. A comparable control group of six pregnant women received the same volume of commercial tea according to the same schedule before vacuum aspiration. Administration of Zoapatle extracts resulted in a menstrual-like cramp and a significant dilatation of the cervix in all subjects studied. In four of the six subjects the menstrual-like pains were associated with bleeding. No comparable effects were observed in the control group. Peroral administration of Zoapatle decocts did not produce any cardiovascular changes, and it did not influence the hematologic status, liver, kidney, and thyroid function, blood lipids, proteins, and electrolyte status. Under the experimental conditions used, Zoapatle extracts did not induce a luteolytic effect judged from the plasma progesterone (and estradiol) levels. It is concluded that peroral administration of freshly prepared decocts of Zoapatle in early pregnancy exerts a distinct uterotonic effect and induces cervical dilatation and uterine bleeding. These changes are not associated with any effect on the plasma levels of progesterone and estradiol or with any untoward side effects.

Abortifacient Agents↗

Rate of metabolism of norethisterone in women from different populations.

The rate of metabolism of orally administered norethisterone was compared in fourteen centres by measuring plasma levels of the steroid by radioimmunoassay at varying times after oral administration of a 1 mg dose. The inter-centre differences were of the same order as the intra-centre differences. Variations in metabolism appeared not to be due to variations in body size.

Adult↗

Effect of graded oral doses of oestradiol on circulating hormonal levels.

A single oral dose of micronized oestradiol (1, 2 or 4 mg) was administered to 10 normally menstruating women on the second day of 3 consecutive menstrual cycles. The order in which the 3 doses were given was chosen randomly for each subject. Samples of peripheral blood were withdrawn on 3 occasions (10, 5 and 1 min) before and on 9 occasions (0.37, 0.75, 1.5, 30, 6.0, 12.0, 24.0, 48.0 and 72.0 h) after the ingestion of oestradiol. Oestradiol, oesterone, oestradiol sulphate, oestrone sulphate, testosterone and LH were measured by means of radioimmunoassays in blood plasma on all occasions. The levels of all oestrogens increased significantly following the ingestion of oestradiol, although to a greatly different extent. The largest and most prolonged increase was seen in the case of oestrone sulphate, the levels of which--depending on the dose ingested--were 20-50 times higher than the pre-treatment levels 3 after the ingestion of the oestradiol capsule. The increase of the levels of oestrone sulphate was still significant (P less than 0.001) after 24 h, and following the ingestion of 2 and 4 mg of oestradiol even after 72 h (P less than 0.05). The levels of oestrone and oestradiol sulphate exhibited smaller increases 3 h after ingestion, i.e. 4-10 and 2.5-5 times, respectively, and the plasma levels of oestradiol showed a minor increase only (1.4-1.8 times). The concentration of oestradiol metabolites studied increased proportionally with the dose of oestradiol administered. On the other hand, a clear-cut dose--effect relationship could not be observed between the amount of oestradiol administered and the plasma levels of LH and testosterone. The data indicate that the bulk of perorally administered oestradiol is transformed to oestrone sulphate accompanied by smaller quantities of oestrone and oestradiol sulphate and that the ratios of circulating oestrogens seen after the ingestion of oestradiol deviate considerably from those observed in the normal menstrual cycle.

Administration, Oral↗