Biomedical subjects

B M Landgren

Publications and source records attributed to B M Landgren.

At least 55 records · Page 3Linked to original sources

PubMed1992

On the intraindividual and gender variability of haemostatic components.

The intraindividual variability in terms of coagulation analyses was explored in 10-16 samples collected from each of 15 women during one menstrual cycle. For comparison, six men were sampled six times during a period of 30 days. The following variables were analysed: FVII, FVIII, FX, vWF:Ag, vWF:ristocetin cofactor, fibrinogen, antithrombin, plasminogen and anti-plasmin. The results demonstrated mean coefficients of variation ranging between 4.5 (plasminogen) and 20.7 (vWF:Ag). In certain individuals, the intraindividual variability amounted to nearly 40%, in particular in the assays of FVIII and vWF:Ag. No direct relation between these two factors and oestradiol, progesterone or testosterone levels could be observed in our individuals. The implications of these variations are discussed in terms of disease prediction and diagnosis of coagulation disorders.

Adult↗

PubMed1992

Progesterone-releasing vaginal rings for use in postpartum contraception. II. Pharmacokinetic profiles in women.

Vaginal rings releasing progesterone with 3 different initial release rates (5, 8 and 20 mg/day) were used by 11, 10 and 10 women, respectively. The period of insertion was 90 days. The 5 and 8 mg/day rings consisted of a core loaded with progesterone, the 20 mg/day ring contained progesterone homogeneously distributed throughout the mass of the ring. Notwithstanding these differences, the total progesterone levels (areas under curve) were directly related to the release rates. So were the rates of decrease of progesterone levels during the 90 days of insertion of the ring. They were 25, 31 and 47% for the rings releasing 5, 8 and 20 mg/day, respectively.

Administration, Intravaginal↗

PubMed1992

Is the contraceptive effect of 300 micrograms of norethisterone mainly peripheral or central?

The effect of norethisterone (NET) on pituitary function was evaluated by measuring circulating follicle stimulating hormone (FSH) and luteinizing hormone (LH) during the mid follicular phase as well as before and after removal of the corpus luteum (CL) in 30 untreated women and 43 women treated with 300 micrograms of NET daily for three months. All untreated women exhibited significantly elevated FSH levels after removal of the CL irrespective of the stage of the luteal phase. In the NET-treated women, the levels of FSH were significantly raised in women with luteal activity but these levels were not influenced by the operative procedure in those women without luteal activity. The LH levels remained unchanged after removal of the CL in both untreated and NET-treated women. The results suggest that a low dose of gestagen exerts variable effects on pituitary function. The main contraceptive effect seems to be through direct interference with ovarian function.

Adult↗

PubMed1992

A prospective, one-year study on the effects of two long acting injectable contraceptives (depot-medroxyprogesterone acetate and norethisterone oenanthate) on serum and lipoprotein lipids.

Two parenterally administered progestins (depot medroxyprogesterone acetate, DMPA, 150 mg/12 weeks and norethisterone oenanthate, NET, 200 mg/8 weeks respectively) were given to women seeking contraceptive advice. Before treatment and after 1, 6, 7, 12 and 13 months blood samples were taken. In serum and in the ultracentrifugally separated lipoprotein fractions the levels of total and free cholesterol, triglycerides and phospholipids were assayed, as were the apolipoprotein A1 and B levels in serum. At the end of the study NET had induced a decrease in all lipid components of the HDL (high density lipoprotein) fraction of approximately 30% and tended to increase LDL (low density lipoprotein) lipids. DMPA also decreased HDL-lipids, approximately 15%. There was also a transient decrease in apolipoprotein A1 after one month in both patient groups. From epidemiological studies it is inferred that low HDL-levels and high LDL-levels are independent risk factors for the development of atherosclerosis and cardiovascular disease. Thus our findings might indicate an adverse effect in this respect of long term treatment with these progestins, particularly with NET.

Adult↗

PubMed1992

The endometrial capillaries during the normal menstrual cycle: a morphometric study.

The areas of the capillary lumen, the entire capillary, the endothelial cells and the adventitia, as well as the thickness of the endothelial cell layer and the adventitia were studied using morphometric methods in endometrial samples from 34 fertile women who had a hormonal profile compatible with normal ovarian function. The biopsies were grouped around the luteinizing hormone surge. The results were calculated as mean values of 72-h periods and related to the mean levels of oestradiol and progesterone circulating in plasma 72 h prior to the biopsy. The results indicated that the sub-epithelial capillary plexus of the human endometrium undergoes dynamic changes during the normal menstrual cycle with a significant dilatation of the vessels during the post-ovulatory phase. A significant correlation was found between the area of the capillary lumen and the mean level of progesterone circulating in the plasma 72 h prior to the biopsy (P = 0.037). We conclude that the ovarian steroids produced during the normal menstrual cycle are likely to influence sub-epithelial vascularization causing dilatation in the post-ovulatory phase. This dilatation of the sub-epithelial capillaries may be related to the development of oedema appearing in the stroma at the time of the expected implantation. The possible functional significance of the capillary dilatation in terms of implantation, however, needs to be further investigated.

Capillaries↗

PubMed1991

The effect of follicular growth and luteal function of "missing the pill". A comparison between a monophasic and a triphasic combined oral contraceptive.

The effects of follicular growth and hormonal indices of the deliberate omission of two low-dose combined oral contraceptives, a monophasic 130 micrograms ethinylestradiol + 150 micrograms desorgestrel) and a triphasic (30 micrograms ethinylestradiol + 50 micrograms levonorgestrel for 6 days, followed by 40 micrograms ethinylestradiol + 75 micrograms levonorgestrel for 5 days and 30 micrograms ethinylestradiol + 125 micrograms levonorgestrel for 10 days) combination during the first three days of one contraceptive pill cycle was studied in two groups of 10 women each. Follicular growth was followed by ultrasound scanning and plasma levels of estradiol, and progesterone were measured every other day until day 19 of the contraceptive pill cycle. In each group, ovulation occurred in one subject and 4 women reacted with follicular activity only, while 5 women on the monophasic and 3 on the triphasic formulation exhibited complete ovarian suppression. Two subjects on the triphasic preparation showed follicular growth followed by insufficient luteal function. Thus, the risk of escape ovulation when the pill-free interval is prolonged to 10 days in women taking low-dose combined oral contraceptive pills, is low (1/10).

Adult↗

PubMed1991

Effects of various IUDs on the composition of cervical mucus.

The influence of three different intrauterine devices on the composition of cervical mucus was studied. The amount of mucin, albumin and immunoglobulin G was estimated. After the insertion of an inert IUD, a decrease in mucin was observed. During copper-IUD use the content of mucin, albumin and IgG was increased in cervical mucus, while weight was not affected. In the levonorgestrel-IUD users, ovulation was inhibited in 2 out of 8 women. Mucus weight was increased. The amounts of mucin, albumin and IgG were not changed. In an in vitro experiment the effect of copper-IUDs on autooxidation of cholesterol was studied. There was an extensive conversion of cholesterol but addition of albumin quenched the oxidation of cholesterol. It is suggested that the increased secretion of albumin induced by copper-IUD users may offer protection against copper-induced cell damage.

Body Weight↗

PubMed1991

Morphometric studies of the endometrium, the fallopian tube and the corpus luteum during contraception with the 300 micrograms norethisterone (NET) minipill.

Biopsy specimen from endometrium, Fallopian tube and corpus luteum were obtained from 35 women treated with 300 micrograms norethisterone daily and from 10 untreated, normally menstruating women. Peripheral levels of LH, progesterone and estradiol were measured. In the norethisterone-treated women four different ovarian reactions were identified. Ovarian activity was completely suppressed (Type A) in 3 women, follicular activity only (Type B) in 10 women, follicular activity was followed by insufficient luteal function (Type C) in 12 women, and peripheral estradiol and progesterone levels compatible with normal ovulation (Type D) in 10 women. The histology of the endometrium varied between atrophy (3 subjects), suppressed proliferation (9 subjects), proliferation (8 subjects), irregular secretory changes (12 subjects) and apparently normal secretory activity (3 subjects). When the histology of endometrium and Fallopian tube was compared with the peripheral hormonal levels and the corpus luteum steroid production in vitra, no correlation was found. Nor was a correlation found between the histologic changes of corpus luteum, endometrium and Fallopian tube. Thus, these target organs seem to react independently to norethisterone treatment.

Adult↗

PubMed1991

Comparative morphometric study of the endometrium, the fallopian tube, and the corpus luteum during the postovulatory phase in normally menstruating women.

OBJECTIVE: To compare function and histologic structure of the corpus luteum (CL) to the morphology of the endometrium and the fallopian tube in normally menstruating women. DESIGN: Circulating steroid and luteinizing hormone (LH) levels were compared with CL steroid production in vitro and the histology of CL, endometrium, and the fallopian tube at four stages of the postovulatory phase (days LH +/- 0/LH+3, LH+4/LH+7, LH+8/LH+11, LH+12/onset of menstruation). SETTING OF PATIENTS: The study included 28 volunteers with proven fertility undergoing surgical sterilization timed in relation to the LH surge. INTERVENTIONS: Blood and urine samples for LH, progesterone (P), and estradiol assessment were obtained before (simultaneously with ultrasound examinations), during, and after operation. Biopsy specimens from CL, endometrium, and fallopian tube were taken at the surgical sterilization and subjected to morphometric analyses. MAIN OUTCOME MEASURES AND RESULTS: Significant correlation was found between the endometrial dating and the LH surge (r = 0.923) and between the dating of the endometrial and CL biopsies (r = 0.918). A significant correlation (P less than 0.01) existed between circulating P levels and two endometrial indices; the number of vacuolated cells (LH+4/LH+7) and the glandular diameter (LH+8/LH+11). CONCLUSION: In normally menstruating women, the endometrial biopsy is likely to closely gauge the CL activity provided the biopsy is timed in relation to the LH surge.

Adult↗

PubMed1991

In-vitro synthesis of steroid hormones in corpora lutea from normal women and women treated with 300 micrograms norethisterone.

The in-vitro oestradiol (E2) and progesterone (P) production by corpora lutea (CL) obtained at sterilization from 30 untreated women and 43 women treated with norethisterone (NET) 300 micrograms daily was measured. The CL were obtained at different stages of the luteal phase in the untreated women [luteinizing hormone (LH) 0 to +3, n = 7; LH +4 to +7, n = 7; LH +8 to +11, n = 9; LH +12 to menses, n = 7] and on days LH +8 to +11 or cycle days 22 to 26 in the NET-treated women. In the treated women, four types of ovarian reaction were identified. Four women showed ovarian reaction Type A (completely inhibited ovarian activity), 14 women Type B (marked follicular activity, but no luteal function), 12 women Type C (normal follicular activity, followed by insufficient luteal function) and 13 women Type D (apparently normal follicular and luteal activity). The CL were incubated in Eagle's medium with and without stimulation by human chorionic gonadotrophin (HCG) for 2 and 4 h. In the untreated women, P and E2 production increased significantly with both incubation time and stimulation by HCG throughout the luteal phase, except in the late luteal phase (LH +12 to menses) where P increased (P less than 0.01) only after 4 h stimulation by HCG. The maximal production of P was found after 4 h incubation with HCG stimulation of CL tissue in the early-mid luteal phase (LH +4 to +7).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Peritoneal fluid volume and levels of steroid hormones and gonadotrophins in peritoneal fluid of normal and norethisterone-treated women.

Peritoneal fluid and blood samples were collected at surgical sterilization from 30 untreated women at various stages of the luteal phase and from 43 women treated with 300 micrograms norethisterone daily. Levels of oestradiol, progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured. The highest peritoneal fluid volume (mean, 23.1 ml) was found in the early luteal phase (LH 0 to + 3) and the lowest (mean, 5.9 ml) in the late luteal phase (LH + 12 to menses). The norethisterone treatment diminished the formation of peritoneal fluid and the degree of inhibition was dependent upon the type of ovarian reaction to norethisterone. Progesterone and oestradiol levels were higher in peritoneal fluid compared to plasma throughout the luteal phase and during norethisterone treatment. A comparison of the levels of these steroids between untreated controls (LH + 8 to + 11) and norethisterone-treated women demonstrated that the progesterone levels in peritoneal fluid were highly reduced by norethisterone treatment, while the oestradiol levels were not affected. The FSH and LH levels were, in contrast to the steroid hormones, significantly lower in peritoneal fluid than in plasma, both in the untreated and the treated women. No differences in the FSH or LH levels between the untreated and treated women were found. The results indicate that the peritoneal fluid volume and the steroid hormone levels in peritoneal fluid vary with the stages of the luteal phase. Norethisterone treatment significantly reduced the peritoneal fluid volume as well as its progesterone concentration, whereas the oestradiol and gonadotrophin levels remained unchanged.

Adult↗

PubMed1991

Plasma estriol levels after intramuscular injection of estriol and two of its esters.

Twelve female volunteers from Berlin and 9 from Stockholm, all using a contraceptive pill (30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel), received an intramuscular injection of estriol (E3; 1 mg in oil) on day 5 of withdrawal bleeding. Blood samples were collected at increasing time intervals during 4 weeks. Three months later, on day 5 of their withdrawal bleeding, 6 women were given intramuscularly (in oil) estriol 3,17-dipropionate (E3-prop) and 15 women estriol 3,17-dihexanoate (E3-hex). The doses were equivalent to 5 mg of estriol, i.e. 6.94 and 8.90 mg, respectively. Blood samples were collected during a period of 9 weeks. Estriol was analyzed by radioimmunoassay in all plasma samples. The average half-life of E3 ranged from 1.5 to 5.3 h after the administration of E3. It was 12.7 h and between 187 and 221 h after the administration of E3-prop and E3-hex, respectively. The average areas under the curve (in nmol.l-1.h) of E3 were between 82.5 and 161 after the administration of E3-prop or E3-hex, and between 27.1 and 37.9 when E3 had been given. As E3 was administered in a 5-fold lower dose than the esters, the areas under curve appeared to be comparable. Thus, the total exposure to E3 seemed to be almost independent of the type of E3 derivatization, while the time and intensity of exposure were very different.

Adult↗

PubMed1990

Mechanism of action of gestagens.

In the mid-1950s it was shown that ovulation can be inhibited by oral administration of progesterone or of synthetic progestogens such as norethynodrel. The idea that progestogens may interfere with fertility even when administered in doses so small, that they do not invariably inhibit ovulation was launched in the mid-1960s by a group of Mexican investigators. Since then a large number of studies have been conducted on the mechanism of action of gestagens when used as contraceptives. The objective of this communication is to review the information collected so far on this topic.

Drug Administration Routes↗

PubMed1990

Pharmacokinetics and biotransformation of orally administered oestrone sulphate and oestradiol valerate in post-menopausal women.

The pharmacokinetic properties and biotransformation of two orally active oestrogens, piperazine oestrone sulphate (PE1S, 2.5 mg/day) and oestradiol valerate (E2V, 2.0 mg/day), given alone or in combination with levonorgestrel (LNG, 250 micrograms/day) were compared in 8 post-menopausal women, using a randomized cross-over design. The end points measured in peripheral plasma included oestrone (E1), oestradiol (E2), oestriol (E3), oestrone sulphate (E1S), oestradiol sulphate (E2S) and oestriol sulphate (E3S). In addition, LNG and sex-hormone-binding globulin SHBG concentrations were also assessed. The plasma levels of E3 were invariably below the detection limit (220 pmol/l). The levels of all the other oestrogens analyzed were consistently higher and the area under the curve significantly greater (except in the case of E3S) following PE1S administration than those recorded after E2V ingestion. The terminal half-lives of the circulating oestrogens measured after PE1S administration did not differ from those found after E2V administration. After 21 days of PE1S administration (in combination with LNG for the last 10 days), the maximum levels of all the oestrogens (except those of E2) were significantly higher than those seen after the first dose. No such difference was observed after E2V administration. There was no difference between the effects of the two treatment regimens with regard to the E1/E2 ratios, but the E1/E1S ratios were significantly lower after PE1S treatment than after E2V administration. It is concluded that, compared with an equivalent dose of PE1S, daily repeated oral administration of E2V yields consistently lower peripheral plasma levels of E2 and its principal metabolites. However, in contrast to PE1S therapy, prolonged administration of E2V does not result in an accumulation of the circulating oestrogens measured.

Administration, Oral↗

PubMed1990

Pituitary, ovarian and endometrial effects of 300 micrograms norethisterone and 30 micrograms levonorgestrel administered on cycle days 7 to 10.

The ovarian, endometrial and pituitary effects of 300 micrograms norethisterone (NET) and 30 micrograms levonorgestrel (L-NOG) administered orally on cycle days 7-10 were investigated in two groups of 10 women each, by daily analysis of plasma estradiol (E2), progesterone (PROG), immunoreactive luteinizing hormone (LH) and follicle stimulating hormone (FSH) in a pretreatment control cycle and during NET or L-NOG administration. Endometrial biopsies were obtained for morphometric analysis on cycle day 11 in the control and treatment cycles. Treatment with 300 micrograms NET resulted in an increase in the area under the E2 peak (p less than 0.05), reduction in the number of subjects with normal progesterone profile (p less than 0.05) and a decrease in the area under the progesterone curve (p less than 0.05). The treatment suppressed the LH peak in 4 subjects and progesterone in 4 subjects. The follicular phase was prolonged in one subject. Norethisterone induced marked subnuclear vacuolation in the endometrium, while the glandular mitoses were decreased during NET treatment. Treatment with 30 micrograms L-NOG resulted in a decrease in subjects with normal progesterone profiles (p less than 0.05) and in the area under the progesterone curve (p less than 0.05). The treatment suppressed the LH peak in 3 subjects and progesterone in 4 women. The follicular phase was prolonged in one subject. L-NOG did not significantly increase the diameter of glands or induce subnuclear vacuolation in the endometrial glands.

Adult↗

PubMed1989

The effect of levonorgestrel administered in large doses at different stages of the cycle on ovarian function and endometrial morphology.

In a pharmacokinetic study, levonorgestrel (L-NOG) 0.75 mg was administered orally to 10 swedish women in the early follicular phase of the menstrual cycle. L-NOG levels were measured after L-NOG administration. A peak level of 16 nmol/l was reached after 2 hours, T 1/2 was estimated to be 14.5 hours (8.5-18.5) in the 24-48-hour interval after dosing. Seventy-two women (in Stockholm, Bombay and Shanghai) were assigned to 4 treatment groups and studied during a control cycle, a treatment cycle and a posttreatment cycle when 0.75 mg L-NOG was administered orally for 4 days in the follicular phase, periovulatory period or luteal phase. Peripheral blood was drawn 3 times weekly during the entire study for the assay of estradiol and progesterone. In 22 women in Stockholm, an endometrial biopsy was obtained on cycle day 20-22 in all 3 cycles studied. When L-NOG was administered on periovulatory days 9, 11, 13, and 15, 3 women showed follicular activity only, 7 exhibited follicular activity followed by insufficient luteal function and 7 women ovulated normally. When L-NOG was administered on periovulatory days 11, 12, 16 and 19, 7 women ovulated during treatment, 6 women exhibited follicular activity followed by insufficient luteal function and 5 exhibited follicular activity only. When L-NOG was administered in the follicular or luteal phase, no effect on ovarian function was seen. No significant prolongation of the cycle lengths was seen when L-NOG was taken during the follicular phase. Only minor effects in the endometrium were observed during treatment.

Adult↗

PubMed1989

Effect of orally administered oestrogens on gonadotrophin levels in post-menopausal women.

The gonadotrophin-suppressing effect of 4 peroral oestrogen regimens (A: 2.5 mg piperazine oestrone sulphate; B: 1.25 mg piperazine oestrone sulphate + 5.0 mg oestriol; C: 2.0 mg oestradiol valerate; D: 10.0 mg oestriol; all administered daily) was studied in 7 post-menopausal women, in the absence, and then in the presence of daily oral doses of 250 micrograms of levonorgestrel. A randomized, complete cross-over design was used, and from each volunteer 80 blood samples were drawn during a period of 252 days for the assay of immunoreactive follicle stimulating hormone (FSH), luteinizing hormone (LH) and bioactive LH levels. All 4 formulations significantly diminished pretreatment gonadotrophin levels. Combination with levonorgestrel enhanced the suppressive effects. Subsequent placebo administration for a week restored gonadotrophin levels to those found previously during oestrogen administration, but not to pretreatment levels. Regimen D exhibited the relatively weakest and regimens A and B the strongest suppression, both in the absence and in the presence of levonorgestrel. Treatment with all oestrogen formulations decreased, and the addition of levonorgestrel increased the ratio of bioactive (B) to immunoreactive (I) LH. Seven days of placebo administration abolished the effect of levonorgestrel, but not that of the various oestrogens on the B/I ratios.

Administration, Oral↗

PubMed1989

Effect of orally administered oestrogens on circulating oestrogen profiles in post-menopausal women.

The effect of 4 peroral oestrogen regimens without and with levonorgestrel (LNG) supplementation (250 micrograms/day) was studied in 7 post-menopausal women. The regimens were: A: 2.5 mg piperazine oestrone sulphate/day; B: 1.25 mg piperazine oestrone sulphate + 5.0 mg oestriol/day; C: 2.0 mg oestradiol valerate/day and D: 10.0 mg oestriol/day. A randomized complete cross-over design was employed and systemic blood levels of progesterone (P), oestrone (E1), oestradiol (E2), oestriol (E3), oestrone sulphate (E1S), oestradiol sulphate (E2S) and oestriol sulphate (E3S) were analyzed. All subjects were consistently post-menopausal, as indicated by low P, E2, E1S and E3S and high FSH and LH levels. The pretreatment and post-treatment levels of E2 and E2S as well as those of E3 and E3S were invariably below detection limit (60 pmol/l and 220 pmol/l, respectively). Treatment with regimens A, B and C resulted in consistently detectable levels of E2, E2S and E3S, but not of E3, and in grossly elevated E1 and E1S levels. Treatment with regimen D gave rise to very high E3S levels. The oestrogen profiles produced by regimens A and C were almost identical, with the exception of higher E1 and lower E3S levels following the administration of regimen A. Combination with LNG did not modify the levels of unconjugated oestrogens, but in certain cases it seemed to diminish those of oestrogen sulphates. A comparison with the results of a preceding study (Aedo A-R et al., Effect of orally administered oestrogens on gonadotrophins levels in post-menopausal women. Maturitas 1989; 11:) reveals that the gonadotrophin-suppressing effect of all 4 regimens still persisted in the post-treatment period at a time when the levels of all oestrogens analyzed returned to those of the pretreatment period.

Administration, Oral↗