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Biomedical subjects

B M Landgren

Publications and source records attributed to B M Landgren.

At least 91 records · Page 5Linked to original sources

Return of ovulation following a single injection of depo-medroxyprogesterone acetate: a pharmacokinetic and pharmacodynamic study.

The effect of a single dose of 150 mg of depo-medroxyprogesterone acetate (DMPA) on pituitary, ovarian and endometrial function was assessed in relation to the peripheral levels of the compound in 8 women. The levels of medroxyprogesterone acetate (MPA), follitropin (FSH), lutropin (LH), prolactin, estradiol (E2) and progesterone ( Prog .) were measured 3 times a week during a pretreatment (control) cycle and then daily during postinjection weeks 14-17, 22-25 and 30-33. An endometrial biopsy specimen was obtained during postinjection weeks 17, 25 and 33. In three out of 8 subjects the daily hormone assays carried out during postinjection weeks 30-33 indicated anovulatory periods; in these subjects peripheral blood was drawn daily during postinjection weeks 46-49 and a fourth endometrial biopsy was taken during week 49.

Adult↗

Pharmacokinetics, pharmacodynamic and endometrial effects of a single dose of 200 mg norethisterone enanthate.

Ovulation was confirmed by daily analyses of the peripheral plasma levels of estradiol (E2)4) and progesterone (P) in a pre-treatment cycle of 14 subjects. An endometrial biopsy was taken either in the proliferative or in the secretory phase of the cycle. On the 5th day of a subsequent cycle 200 mg norethisterone enanthate (NET-EN) was administered intramuscularly. The levels of E2, P and those of NET were analyzed during the next 19 days and again during 44-60 days following the injection. The endometrial biopsy was repeated on the 23rd and 59th day of the treated cycle. The levels of NET reached a peak of 34.3 nmol/1 on the sixth post-injection day and decreased to below detectable limits in 3 of 12 subjects by the end of the observation. Ovarian activity was completely suppressed in all women during the first period, but returned to different levels in 11 subjects during the second. Four of them exhibited ovulatory steroid pattern. The morphologic changes of the endometrium reflected the progestogen effect in the first post-injection period but were characteristic of the ovarian reaction in the second.

Adult↗

Normal variation in the length of the follicular phase of the menstrual cycle: effect of chronological age.

Normal probability plots were used to analyse the distribution of follicular phase length in a population of 293 apparently ovulatory menstrual cycles from women aged between 18 and 39 years. The length of the follicular phase was defined as the interval (in days) from the onset of menstruation up to, but not including, the day of the LH peak. Follicular phase length appeared to be log-normally distributed and graphical inspection of the probability plot suggested that the geometric mean (and 95% confidence limits) of follicular phase length in this study group was 12.9 (10.3 to 16.3) days. There was a significant decrease (P less than 0.001) in follicular phase length with chronological age, from 14.2 days in women aged 18-24 years to 10.4 days in women aged 40-44 years.

Adolescent↗

Normal variation in the length of the luteal phase of the menstrual cycle: identification of the short luteal phase.

Normal probability plots were used to assess the homogeneity of a population of 327 luteal phases from apparently ovulatory menstrual cycles. The length of the luteal phase was defined as the interval (in days) following but not including, the luteinizing hormone peak, up to and including the day before onset of menstruation. A small sub-set of the population consisted of cycles with abnormally short luteal phases but the majority of the data followed a normal frequency distribution which gave a mean (+/- SD) for normal luteal phase length of 14.13 (+/- 1.41) days. It was estimated that all cycles with a luteal phase less than or equal to 9 days were abnormal, and that 74%, 22% and 2% respectively of cycles with luteal phases of 10, 11 and 12 days were also abnormal. The total incidence of short luteal phases defined as above was 5.2%.

Adolescent↗

The short luteal phase and infertility.

The distribution of the length of the luteal phase was investigated in 187 women with regular, apparently ovulatory menstrual cycles of whom 95 had unexplained infertility and the other 92 comprised a group of healthy volunteer subjects. If the short luteal phase is associated with infertility it might be expected to occur more frequently in women with unexplained infertility. A short luteal phase (defined as a luteal phase lasting less than or equal to 11 days) was found in 9% of the infertile group and in 8% of the normal group showing that these cycles do not occur more frequently in women with infertility.

Female↗

Changes in soluble proteins in cervical mucus during midcycle in normally menstruating women.

Albumin, IgG and complement C3c were analyzed by immunonephelometry in cervical mucus collected daily at midcycle. There was a statistically significant difference in the amount of mucus recovered on the day of the luteinizing hormone (LH) surge and on the following day. Several nadirs in protein concentration could be visualized in 8 out of 14 subjects, whereas in 6 subjects, no such changes in concentration were found. In terms of soluble protein concentrations and amounts there were no differences between cycle days. For changes in soluble protein concentrations and amounts, no systematic time relation to the LH peak could be found.

Adult↗

Effects of repeated sampling on the properties of the cervical mucus during one day at midcycle.

Midcycle cervical secretions were collected every hour from 08.00 to 12.00 h in 12 normal women. There was a significant decrease in gram wet weight of mucus in the first four samples followed by an increase in the fifth specimen (trend analysis). Spinnbarkeit decreased significantly during repeated sample collection. Albumin concentration in cervical secretion increased significantly during repeated sample collection, but there was no statistically significant difference in the total amount of albumin recovered during repeated sample collection. The possibility of a hormonal regulation of the water content in the cervical mucus is discussed.

Adult↗

A method for isolation, characterization, and quantitation of soluble proteins in uterine cervical secretion.

By sodium chloride (0.66 M) extraction of cervical mucus on an inert chromatographic bed, soluble proteins can be conveniently recovered. Individual proteins such as albumin and IgG may then be quantitated by immunonephelometry. The procedure has been shown to improve reproducibility which is very poor in the presence of mucin. By concentrating the NaCl extract by centrifiltration, proteins present in low concentrations - such as complement C3 - can be measured. The concentrate has also been used for analyses by isoelectric focusing or gradient gel electrophoresis on polyacrylamide gels.

Adult↗

Pituitary, ovarian and endometrial effects of progesterone released prematurely during the proliferative phase.

The pituitary, ovarian and endometrial effects of premature exposure to progesterone during the proliferative phase were investigated in 18 normally menstruating women. Daily blood samples were drawn during a control cycle and an endometrial biopsy was obtained on cycle day 6 (in 9 subjects) and on cycle day 11 (in 9 subjects), respectively. Daily blood samples were drawn again throughout a treatment cycle, in which a vaginal delivery system releasing progesterone at a constant rate of 1.4 mg/24 h was inserted and left in situ for 96 hours during cycle days 2-6 (9 subjects) and cycle days 7-11 (9 subjects), respectively. On the 6th and 11th cycle day, respectively, the devices were removed and another biopsy specimen was obtained. In all blood samples the levels of immunoreactive lutropin (LH), estradiol (E2), 17-hydroxyprogesterone (17-HO-P), progesterone (P) and 20 alpha-dihydroprogesterone (20 alpha-HO-P) were estimated by radioimmunoassay. Insertion of the devices resulted in a rapid, approximately six-fold increase (from 0.5 to 3.0 nmol/l) in P levels and an approximately three-fold (from 0.5-0.6 to 1.5-2.0 nmol/l) increase in 20 alpha-HO-P levels. A high degree of correlation was found between P and 20 alpha-HO-P levels. No major changes were observed in the profiles and levels of the other hormonal indices studied. However, premature exposure to small amounts of P during cycle days 2-6 resulted in a significant decrease in the ratio of the E2 to LH peaks and exposure during cycle days 7-11 gave rise to a significant increase in the ratio of the length of follicular to luteal phases. Progesterone released during the early proliferative phase (days 2-6) exerted little, if any, effect on the appearance of the endometrium. However, the same dose of P released during the late proliferative phase (days 7-11) significantly diminished the number of glandular mitoses, the height of the glandular epithelium, reduced pseudostratification and the number of plasmolemmal vesicles, but did not induce any subnuclear vacuolation, predecidual reaction or leucocytic infiltration. It is suggested that systematic studies involving the exposure to progestogens in normally menstruating women during cycle days 7 to 11 will provide a reliable and practical method for the comparative assessment of the potency profile of individual progestogens in women.

17-alpha-Hydroxyprogesterone↗

Pharmacodynamic effects of ethinyl estradiol in women using vaginal devices releasing small doses of levonorgestrel at a constant rate.

Eight normally menstruating women were provided with vaginal devices releasing levonorgestrel (NOG)4) at a constant rate of 20 micrograms/24 h. On day 71 or 72 following the insertion of the device, oral doses of 50 micrograms of ethinyl estradiol (EE) were administered daily for one week. Peripheral blood samples were drawn three times weekly during a pretreatment (control) cycle and from day 29 of the treatment period. The levels of progesterone (P), estradiol (E2) and NOG were measured by radioimmunoassay, sex hormone binding globulin (SHBG) by a steady state polyacrylamide gel electrophoresis and the percentage of binding of NOG, testosterone (T) and E2 by equilibrium dialysis of diluted plasma. An endometrial smear and a biopsy were taken from each subject on 3 occasions, viz. during the control cycle (cycle day 20-22), during the period with the NOG-releasing device in situ (44-50 days after the insertion of the device), and on the 7th day of concomitant EE administration.

Adult↗

Evaluation of a rapid method for determination of total urinary estrogens in morning samples from normally menstruating women.

Total urinary estrogens (TUE) in morning urine samples delivered during seven days around midcycle from 14 normally menstruating women were analyzed and the results were compared with those obtained by radioimmunoassay of serum estradiol-17 beta (E2) and LH. The Spinnbarkeit of the cervical mucus was also determined daily and ovulation was confirmed by RIA of serum progesterone. Significant correlations (p less than 0.01) between day of peak levels of serum E2 and the day with the highest TUE value were obtained. Peak values for Spinnbarkeit, estradiol, TUE and LH were on the average obtained on cycle day 13.1 (10-17), 13.3 (10-16), 13.9 (11-18) and 14.1 (11-17), respectively, and the mean cycle length was 27.9 (24-32) days. The difference in mean peak day for estradiol and TUE, estradiol and Spinnbarkeit, estradiol and LH was significant in each comparison (p less than 0.01). Assays of TUE in morning samples as compared to analysis of TUE in 24 h urine portions were compared during 48 h in 10 women. The day with the highest TUE excretion was found to be the same in 7 women irrespective of the type of urinary sample analyzed. Analysis of urinary creatinine did not improve the TUE results. Levels of TUE in normally cycling females (n = 14); in women taking contraceptive steroids (n = 10), in menopausal women (n = 10) and in normal men (n = 10) agreed with those previously reported. It is concluded that the TUE determination by RIA may be helpful as a rapid method for everyday clinical use.

Adult↗

The effect of a prostaglandin synthetase inhibitor on the hormonal profile and the endometrium in women.

A prostaglandin synthetase inhibitor, naproxen, was given continuously throughout the menstrual cycle at a dose of 250 mg b.i.d. to 10 healthy fertile women. Blood samples were drawn three times a week during an earlier control cycle and during the treatment cycle and analyzed for LH, FSH, prolactin, estradiol and progesterone. Endometrial biopsies were taken in the secretory phase. Naproxen treatment did not suppress ovulation in any of the cycles and did not affect the corpus luteum function. In only one of the endometrial samples taken was the density of the lysosomes increased in the treatment cycle compared with the control cycle.

Endometrium↗

A preliminary pharmacological trial of the monthly injectable contraceptive cycloprovera.

A comparative pharmacological pilot study of the monthly injectable contraceptive CycloProvera was carried out in 11 women in four centres. There were no significant differences in the results between the centres except that the injection-bleeding interval appeared to be shorter in Swedish women than in those in Havana and Mexico. Medroxyprogesterone acetate was detectable in blood for 28 to 62 days after injection of CycloProvera and although follicular activity returned in less than 28 days after injection in many of the women, corpus luteum function was suppressed for at least seven weeks in all women. Most of the women retained a regular menstrual pattern; six of 33 cycles were amenorrhoeic. There was no significant change in any of the biochemical and haematological analyses.

Adult↗

Pharmacokinetic and pharmacodynamic investigations with vaginal devices releasing levonorgestrel at a constant, near zero order rate.

The pharmacokinetic and pharmacodynamic effects of vaginal devices releasing levonorgestrel (L-NOG) at a constant rate (in vitro release: approximately 20 micrograms/day) were studied in a group of 20 normally menstruating women during a period of 90 days of continuous use. Peripheral blood samples were withdrawn two or three times (in the great majority of subjects, on Mondays, Wednesdays and Fridays) during a pretreatment (control) cycle, during 90 days of exposure and during the first week following the removal of the device, and the levels of L-NOG, estradiol and progesterone were analyzed by radioimmunoassay techniques. In 8 of these subjects, endometrial biopsies were also taken during days 23 to 25 of the control cycle, and then 6 and 10 weeks following the insertion of the devices. In addition, the initial absorption rate and removal half-life of L-NOG were assessed in 7 subjects using the devices for a period of 8 days only. Following insertion of the devices, the levels of L-NOG rose very rapidly, and reached the final "plateau" in some 30 minutes' time. This was followed by a limited period of "burst" with doubling the levels for a few hours, after which the levels remained stable and diminished very slowly in a linear fashion with an average decline of 23-26% during 90 days, corresponding to a daily decrease of 0.2 to 0.3 per cent. The removal half-life (first compartment) after 90 days of exposure in 19 subjects was 16.1 (13.7-18.6) hours. Sixty-nine treatment segments of 30 days were studied with frequent hormone assays; of these, 20 (or 29%) were anovulatory, 13 (19%) exhibited inadequate luteal function, and 32 (52%) had normal ovulatory-like cycles. All endometrial biopsies obtained during the pretreatment cycle were normal secretory; of the 16 biopsies obtained during treatment, 4 were suppressed, 2 proliferative, 6 secretory, and 4 could not be dated because of bleeding. An assessment of the bleeding profiles during exposure to L-NOG revealed almost a doubling of the number of days with bleeding and spotting (35% compared to 18% during the pretreatment cycle). However, significantly more frequent bleeding was found in the 20 anovulatory segments (37.3%) than in the 36 normal ovulatory-like ones (27.7%). It is concluded that differences in the frequency of bleeding and spotting with low-dose progestogens may reflect differences in the frequency of ovulation inhibition just as much as differences in the hormonal profiles of the compounds administered.

Adult↗

Effects of ethinyl-estradiol/noretisterone combinations on serum lipoproteins.

Eleven healthy young women (age range 20-28 years) were given three different oral contraceptives (OCs) in random order, each contraceptive for 3 months. Smoking, eating, drinking and habits of physical activity were similar throughout the study period. The combinations were: ethinyl-estradiol/noretisterone (EE/NET) 35 micrograms/0.5 mg, 35 micrograms/1 mg and 50 micrograms/1 mg. The 35/0.5 and the 50/1 EE/NET combinations led to significant weight increases of 2.4 and 1.7 kg, respectively. All EE/NET combinations produced LDL-TG increases, from a pretreatment value of 0.28 +/- 0.04 (SD) mmol/l to 0.34 +/- 0.07, 0.35 +/- 0.06 and 0.42 +/- 0.13 mmol/l (P less than 0.01 for all). LDL-cholesterol increased from 2.99 +/- 0.63 mmol/l to 3.35 +/- 0.62 (P less than 0.01) after 35/1 treatment and to 3.43 +/- 0.62 mmol/l (P less than 0.001) after 50/1 treatment. These two EE/NET combinations also caused significant reductions of HDL-cholesterol, in both cases from a pretreatment value of 1.75 +/- 0.16 mmol/l to 1.64 +/- 0.24 mmol/l (P less than 0.05). Since all values after EE/NET treatment remained well within normal ranges, these low-dose OCs probably have little effect on the development of atherosclerosis due to serum lipoprotein abnormalities. However, our findings suggest that OCs may interfere with the cholesterol ester/TG exchange between LDL and HDL.

Adult↗

Morphometric analysis of the human endometrium in relation to peripheral hormone levels.

Twelve indices were quantitated at three sites in 68 endometrial biopsies from 14 women in five cycles each in which daily plasma levels of luteinizing hormone (LH), estradiol (E2), and progesterone (P) were measured. It was found that a single biopsy specimen is representative of the entire endometrium. Using classic dating, 59% of the biopsies were correct. The error rate increased with the distance from the LH surge. The morphometric indices revealed significant differences am ong all 48-hour secretory phase periods except days LH + 7 to LH + 10. The glandular diameter was positively correlated with proliferative phase E2 levels and with secretory phase P levels; the latter were negatively correlated with stromal mitoses. Basal vacuoles were negatively correlated with E2 and positively with P levels.

Adult↗