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Biomedical subjects

E Johannisson

Publications and source records attributed to E Johannisson.

At least 37 records · Page 2Linked to original sources
PubMed1993

Morphological characteristics of preimplantation stage endometrium in the rhesus monkey.

The morphological characteristics of endometrium on day 6 after ovulation of conception (group 1) and non-fecund, menstrual (group 2) cycles have been studied in the rhesus monkey (n = 30). A conception cycle was distinguished by the presence of a developmentally normal, age-stage-synchronized embryo. Thus, 78% of the mated cycles (n = 18) yielding synchronous embryos (12 zona-encased and two zona-free blastocysts) were used for this study. On day 6 after ovulation, no significant changes in the serum concentrations of oestrogen and progesterone were seen in conception cycles (n = 14) compared with the non-mated, normal ovulatory cycles (n = 12). Morphometric analyses revealed that on day 6 of gestation (n = 8), endometrium differed from the corresponding non-mated luteal phase (n = 7) with significant increases in epithelial mitosis (P < 0.01), height of glandular epithelium (P < 0.05), volume ratio of gland cell to gland (P < 0.03), degree of pseudostratification (P < 0.02), and higher frequency of supranuclear, adluminal accumulation of vacuoles in gland cells (P < 0.05). The degree of stromal oedema was higher (P < 0.02) in fecund cycles but there was no change in venular diameter. In a separate set of experiments, estimates of tissue vascular response revealed a higher (P < 0.02) endometrial extravascular albumin space on the same day of gestation; there were no differences, however, in endometrial blood volume, or in the number of von Willebrand antigen-positive capillaries and small vessels between the two groups (group 1, n = 6; group 2, n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of tamoxifen alone and in combination with RU 486 on the endometrium in the mid-luteal phase.

The effects of RU 486 combined with tamoxifen and tamoxifen alone on hormonal parameters and endometrial development at the time of implantation were studied. Measurements of cytosolic oestrogen and progesterone receptors in endometrium and placental protein 14 (PP14) in plasma were also included. Three dosage schedules were used: single oral dose of 40 mg tamoxifen alone and in combination with 200 mg RU 486, and 40 mg tamoxifen for three consecutive days starting on the first day after the luteinizing hormone (LH) surge. The combined treatment prolonged the luteal phase (P < 0.05) and increased the plasma levels of progesterone. A single dose of tamoxifen did not affect the bleeding pattern and plasma hormone levels, but raised plasma oestradiol and LH with the 3-day treatment. The endometrium was retarded after the combined and the 3-day treatment with tamoxifen. Concentrations of cytosolic progesterone receptors were higher after the combined therapy, but were unaffected after tamoxifen only. PP14 levels were higher (P < 0.05) after repeated tamoxifen doses than in controls, but were lower with combined treatment. Progesterone and oestrogen are evidently necessary for endometrial maturation during the secretory phase of the menstrual cycle. PP14 levels in plasma cannot be used for clinical assessments of endometrial function because high levels coincide with disturbed endometrial development.

Embryo Implantation↗
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

Morphometric study of the human endometrium following continuous exposure to levonorgestrel released from vaginal rings during 90 days.

The effects of vaginal devices releasing levonorgestrel (LNG) at a constant rate of approximately 20 micrograms/24 hrs on the human endometrium were studied in a group of 69 normally menstruating women during a period of 90 days of continuous use. Peripheral blood samples were withdrawn three times weekly starting at day 10 of a pretreatment (control) cycle and then three times weekly from day 60 to 90 of the treatment period. The levels of LNG, estradiol, progesterone and sex hormone binding globulin (SHBG) were analyzed by radioimmunoassay techniques. Endometrial biopsies were obtained in the luteal phase of the pretreatment cycle and on day 84-87 of the treatment period. Increased bleeding occurred in most subjects exposed to the LNG-releasing device; the mean number of bleeding and spotting days was 26.4 +/- 8.9 S.D. which exceeded that found in their control cycle. Morphometric analyses of the endometrial biopsies using 9 quantitative indices, revealed highly significant changes in glands and stroma following the use of the LNG-releasing vaginal device. Irrespective of the circulating steroid levels, the administration of LNG significantly diminished the glandular diameter (p less than 0.001), reduced the volume density of the glands (p less than 0.001) and of the glandular epithelium (p less than 0.001). and modified the ratio glandular epithelium: glands (p less than 0.001). It is concluded that levonorgestrel released at a rate of 20 micrograms/24 hrs, induces characteristic changes in the histologic structure of the human endometrium. Although no simple correlation has been found between any of the endometrial indices and the numbers of bleeding/spotting days or bleeding days, the changes as such may represent biochemical alterations which could be predisposing factors for intermenstrual bleeding and spotting. To prove a causal relationship between morphological and biochemical changes and changes in bleeding patterns, further in-depth studies may be required.

Contraceptive Agents, Female↗
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↗
PubMed1990

Effects on the endometrium, endo- and exocervix following the use of local progestogen-releasing delivery systems.

Some conflicting reports have appeared in the literature as to the effect of progestogens on the endometrium and on the endo- and exocervix in animals and humans. Hyperplasia of the endometrial and endocervical epithelium has been reported in some non-human primates following the administration of progestogens. In other studies no evidence has been found for such changes. In women using combined oral contraceptives, it has been claimed that the progestogen component causes adenomatous hyperplasia of the endocervix and that this hyperplastic transformation could be a precursor to adenocarcinoma of the cervix. So far, there is, however, no evidence in the literature to confirm this hypothesis. In view of the development of new delivery systems with a constant release of small amounts of progestogens, previous reports in the literature on hyperplasia and potential malignant transformation of the endometrium and the endocervix have been a matter of concern. The aim of the present study is therefore to review results from studies in animals and humans in particular with reference to the effect of a local release of various progestogens on the endometrium and the endo- and exocervix.

Animals↗
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↗
PubMed1990

The effect of RU 486 administered during the early luteal phase on bleeding pattern, hormonal parameters and endometrium.

The purpose of the present study was to investigate the effect of a single dose of RU 486 administered very early in the secretory phase on endometrial development and levels of progesterone receptors, on plasma levels of gonadotrophins and ovarian hormones and on the pattern of menstrual bleeding. Twenty-four regularly menstruating subjects participated and were studied during a control, a treatment and a follow-up cycle. In the treatment cycle, a single dose of 200 mg RU 486 was given in the evening of the second day after the urinary LH peak. Plasma was collected from cycle day 10 until menstruation in both control and treatment cycles. The lengths of the control, treatment and follow-up cycles were equal. Three of the subjects had slight vaginal bleeding in association with RU 486 intake which, however, did not disturb their normal menstrual rhythm. Plasma levels of oestradiol, progesterone and FSH were not affected in the treatment cycle, whereas LH levels increased slightly. The elimination half-life of RU 486 was 28.6 h. An endometrial biopsy was taken 12, 36 or 84 h (LH + 3, LH + 4 and LH + 6) after drug intake (eight subjects in each group) and another biopsy was taken on the corresponding day in the control cycle. The specimens were assessed by morphometric analysis and for cytosolic progesterone receptor concentrations. Endometrial biopsies taken 12 h (on LH + 3) after RU 486 intake contained significantly (P less than 0.001) lower levels of cytosolic progesterone receptors than in the control cycle, but levels at 36 and 84 h were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

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

In an attempt to identify factors that may be responsible for reproductive failure, we compared endometrial biopsies taken from infertile patients during the luteal phase of spontaneous cycles (n = 18) with those taken after ovarian stimulation (n = 18). Morphometric analyses were performed and compared with peripheral estradiol (E2) and progesterone levels at the time of supposed implantation. In stimulated cycles the number of glands per square millimeter was positively correlated to the E2 level. The morphometric data point to a measurable difference between the study groups, indicating an insufficient secretory transformation of the tissue in infertile women when compared with a group of fertile women. The observations suggest that hormonal stimulation occasionally results in impaired development of the endometrial glands.

Adult↗
PubMed1989

Vascular changes in the human endometrium following the administration of the progesterone antagonist RU 486.

Eleven healthy women were assigned to one of two groups. They received 50 mg RU 486 orally per day either on cycle days 7 to 10 (preovulatory group n = 5) or on cycle days 20 to 23 (postovulatory group, n = 6). An endometrial biopsy was taken on the fourth day of the RU-treatment in the preovulatory group and on the second (n = 2) or fourth (n = 4) treatment day in the postovulatory group. Biopsies from 34 untreated women representing matched samples from early and mid preovulatory phase (n = 10) and mid and late postovulatory phase (n = 24) were used as control. The ultrastructure of the endometrial capillaries was investigated by morphometric methods. The administration of RU 486 during the preovulatory phase did not modify the vascular structure. However, when given in the postovulatory phase, necrosis occurred in the capillary endothelial cells with and without regressive changes of the adjacent stroma. The area and diameter of the capillary lumen and the area of the adventitia was smaller than in the control material (p less than 0.01). The result of the study suggests that RU 486, when administered in the postovulatory phase, directly affects the capillary vessels of the endometrium.

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↗
PubMed1988

Endometrial and vaginal response to three different oestrogen preparations administered by the transdermal and oral routes.

In a randomized, cross-over study endometrial and vaginal response to transdermal 17 beta-oestradiol (TTS-oestradiol 50 micrograms) and two forms of oral oestrogen replacement therapy (conjugated oestrogens 1.25 mg and oestradiol valerate 2 mg) were studied in 13 peri-menopausal and post-menopausal women. Five (5) of the women exhibited periodic ovarian function as evidenced by peripheral oestradiol and progesterone levels and were considered to be peri-menopausal. In the post-menopausal group of 8 women the bleeding pattern was more regular than among the peri-menopausal women. In the case of the post-menopausal group the number of days on which spotting and bleeding occurred was significantly lower during the administration of TTS-oestradiol than during treatment with conjugated oestrogens. This finding was paralleled by a significantly higher karyopyknotic index in the vaginal epithelium and significantly increased deoxyribonucleic acid (DNA) synthesis in the endometrial cells during treatment with equine oestrogens. No significant difference was seen in these indices when the effect of TTS-oestradiol was compared with that of oestradiol valerate. The study results in the post-menopausal group suggested a relationship between the intensity of the oestrogen treatment and not only the proliferation and maturation of the oestrogen target-organ cells but also the number of days on which bleeding occurred. It was concluded that a clear distinction needs to be made between peri-menopausal and post-menopausal women. In the present study the irregular ovarian activity among the peri-menopausal subjects precluded an unbiased assessment of the exogenous oestrogens. It is also likely that exogenous oestrogens exert a cumulative action with oestrogen secreted endogenously, interfere with the physiological events at the target organ level and induce uncontrollable endometrial bleeding. The complete cessation of ovarian activity may therefore have to be established before exogenous oestrogens are administered to climacteric patients.

Administration, Cutaneous↗