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Biomedical subjects

G Cullberg

Publications and source records attributed to G Cullberg.

At least 19 recordsLinked to original sources

Pregnancies with growth-retarded twins in breech-vertex presentation at increased risk for entanglement during delivery.

The purpose of this population based study on twins born in Sweden between 1961 and 1987 was to estimate the risk to the fetuses of becoming entangled during birth, and to identify those pregnancies with an increased risk for this rare complication. By using 3 separate questionnaires, 41 of 26,428 twin pregnancies with entanglement were identified. Twins in breech-vertex presentation (group A; 29 cases) were at significantly greater risk of entanglement (chi 2 = 168.3, p less than 0.001) than twins not in breech-vertex presentation (group B; 8 in vertex-vertex, 3 in breech-breech, and 1 in vertex-breech presentation). Known risk factors for entanglement in group A were intra-uterine growth retardation, a birth weight less than 2000 g, and antenatal fetal death. Intrapartum-neonatal mortality reached 38.9% in group A (median gestational week 36); and for group B, 8.3% (median gestational week 38). Entanglement during the study period occurred in 1 of 645 twin deliveries, on average. A vaginal delivery is proposed for women with twins in breech-vertex presentation, unless other risk factors leading to an increased risk for entanglement warrant abdominal delivery.

Birth Weight

Vaginal administration of low-dose oestradiol--effects on the endometrium and vaginal cytology.

Twenty (20) post-menopausal women, mean age 62.4 yr, presenting with symptoms associated with urogenital atrophy were treated intravaginally with daily doses of 25 and 50 micrograms oestradiol (E2) in a double-blind, cross-over study. After randomization, the patients started daily treatment with pessaries containing either 25 or 50 micrograms E2 for 3 wk, followed by a maintenance period of 6 wk during which the pessaries were used only twice a week. A 4-wk wash-out period was followed by another treatment period of 9 wk. The effects on the karyopyknotic index (KPI) and on endometrial histopathology were assessed before and after 3, 9, 16 and 22 wk of treatment. In the case of the 25 micrograms dose the mean KPI values were 34.7 and 20.9% after 3 and 9 weeks of treatment, respectively, the corresponding figures after treatment with 50 micrograms E2 being 39.2 and 22.7%. No dose-effect relationship was apparent from the vaginal cytology findings. Endometrial biopsies could not be taken systematically in all patients. Weak proliferation of the endometrium was observed in 1 woman after 3 wk of daily treatment with the 50 micrograms dose. No endometrial stimulation was detected in any of the patients after treatment with 25 micrograms daily. Beneficial clinical and cytological effects were obtained with both dosage regimens. Daily intravaginal administration of 25 micrograms E2 can accordingly be advocated for the treatment of urogenital symptoms attributable to oestrogen deficiency in post-menopausal women.

Administration, Intravaginal

Anthropometric variables and metabolism in polycystic ovarian disease.

Anthropometric, endocrine and metabolic variables, were examined in women with polycystic ovarian syndrome (PCO), and in normal control women. Obese women with PCO had higher plasma insulin values than non obese women with PCO, but lean body mass, glucose tolerance, plasma triglycerides and blood pressure were not different in spite of almost twice the body fat mass in the obese PCO women. However, in comparisons between non-obese PCO and control women, with equal body fat mass, the PCO women had higher blood pressure, plasma triglycerides and insulin, as well as a tendency to increased lean body mass. Both PCO groups had a high waist/hip ratio and larger abdominal fat cells than controls, indicating a preferential abdominal accumulation of adipose tissue. In comparison with abdominal adipocytes, femoral adipocytes were larger and had higher lipoprotein lipase activity in the control women, while in the PCO women these regional differences were not found. Basal and norepinephrine stimulated lipolysis were higher in the abdominal than femoral adipocytes in all groups. Substitution of the PCO women with ethinyl estradiol plus desogestrel during 6 months resulted in a regression of clinical androgenic symptoms as well as a normalization of plasma concentrations of free testosterone and sex hormone binding globulin. However, neither body composition nor metabolism were normalized. It was concluded that body fat distribution is more closely related to hypertension and metabolic derangements than total fat mass in the PCO syndrome. It is suggested that the relative paucity of femoral adipose tissue is due to a lack of specific effects of progesterone on adipocytes in this region.

Adipose Tissue

Ethinylestradiol and desogestrel, alone or in combination with two doses of estriol. Effects on plasma proteins.

Nineteen fertile women were treated with three differently composed oral contraceptives in a cross-over study and were randomly allocated to begin with one of the three preparations. The tablets contained 0.030 mg ethinylestradiol +0.15 mg desogestrel alone (A) or in combination with either 0.5 mg estriol (B) or 2 mg estriol (C). After two treatment cycles on each preparation, blood samples were obtained and analysed for ceruloplasmin, SHBG, prealbumin, transcortin and thyroxine-binding globulin. No differences were found in the induction of liver protein synthesis. It was concluded that the addition of estriol in doses of 0.5 or 2 mg did not influence the effects induced by ethinylestradiol.

Adolescent

Fat-soluble 17 beta-estradiol: a way of reducing dosage in steroid hormonal substitution?

Eight ovariectomized women were given 0.5 mg 17 beta-estradiol cyclo-octyl acetate (E2COA) dissolved in arachis oil + 0.15 mg desogestrel, and 2 mg micronized 17 beta-estradiol (mE2) + 0.15 mg desogestrel orally in a crossover fashion for 20 days each. The preparations were taken on 10 days together with a meal, on 10 days 3 hours after a meal. Blood samplings were performed 3 h after capsule ingestion for analysis of serum estradiol (S-E2), estrone (S-E1) and sex hormone binding globulin (SHBG). Before treatment, all women had climacteric complaints. During treatment these symptoms were alleviated and no discomfort was reported. No differences in serum levels of estrogens were found in either of the preparations when capsules were taken with or without food. However, serum levels of E2 were found to be 100% higher per mg substance given after E2COA vis-à-vis mE2. This indicates either a delayed breakdown and/or a better resorption. The E1/E2 ratio after E2COA was only half that after mE2 intake. This hints at another route of resorption. SHBG concentrations were somewhat elevated following mE2 administration, whereas a slight decrease was found after E2COA. The resulting post-treatment difference was significant, suggesting a less estrogenic liver effect by E2COA. No accumulation of E2 or E1 was seen after either of the preparations. Our findings support the hypothesis that E2COA, being fat soluble, is resorbed via the lymphatic system. By avoiding the first liver pass the dosage of estrogen can be halved.

Aged

Ovulation inhibition with 17 beta-estradiol cyclo-octyl acetate and desogestrel.

Ovulation inhibition and bleeding control with a combination of 0.5 mg 17 beta-estradiol cyclo-octyl acetate (E2COA) and 0.15 mg desogestrel was investigated in 10 regularly menstruating women for 21 days. In half the group the treatment was extended for 7 days (days 22-28) with 0.03 mg desogestrel in order to evaluate any posttreatment influence on the gonadotropin levels. E2COA, beeing a long-chain fatty ester dissolved in oil, was expected to be resorbed from the intestinal wall via the lymphatic system. By incorporating it in the chylomicrons, E2COA would thereby avoid the unfavourable first liver pass. The serum levels of progesterone were suppressed during treatment. No increase in 17 beta-estradiol (E2) concentration was found; levels remained low and even during medication. No peak values of gonadotropins were seen. Thus follicular hormonal activity and ovulation was inhibited by this combination. Bleeding control was, however unacceptable in all volunteers. The addition of desogestrel during the fourth investigation week apparently did not induce any hormonal differences. The estrogenic activity is shown by the low, even S-E2 levels, but the dosage of E2COA seems to be too low in relation to progestogen dosage. Further studies will have to be performed in order to find the ideal combination.

Adult

Second trimester abortion by rivanol with or without cervical dilatators. A randomized comparison.

Fifty women undergoing second trimester legal abortion were randomly assigned to one of three groups: 1. given Rivanol and left with balloon catheter in the cervical canal with addition of oxytocin infusion. 2. same treatment as above but catheter removed and replaced by a Lamicel cervical dilatator, 5 mm in diameter; 3. as group 2, but with a 6 mm Laminaria tent inserted. Induction-abortion interval and need for analgesics were recorded, as well as possible side effects and complications. No statistical differences were found between the three groups for any of the parameters. We have thus not been able to show any advantages of using Laminaria or Lamicel osmotic cervix dilatators in second trimester abortions.

Abortion, Induced

The relative fatty acid composition of serum lecithin and cholesterol ester: influence of an estrogen-progestogen regimen in climacteric women.

The relative fatty acid compositions of serum lecithin and cholesterol ester were studied during continuous treatment with an estrogen/progestogen combination. All 26 women who participated suffered from climacteric complaints and were given one tablet daily containing 2 mg of 17 beta-estradiol, 1 mg of estriol, and 1 mg of norethindrone acetate. Blood samples were taken before treatment and after 3 and 12 months of treatment. In serum lecithin, a decrease (p less than 0.01) in stearic acid concomitant with an increase of linoleic (p less than 0.05) and arachidonic (p less than 0.01) acids was recorded. The most evident changes noted in cholesterol ester were decreased levels of stearic (p less than 0.01), oleic (p less than 0.05), and arachidonic (p less than 0.001) acids. Polyunsaturated acids of the n-6 series are precursors for prostaglandins and leukotrienes. In the present study an increase of dihomo-gamma-linolenic, linoleic, and arachidonic acids in serum lecithin was found after treatment, and theoretically this finding may have an impact on the prostacyclin-thromboxane balance.

Adult

Effects of a low-dose desogestrel-ethinylestradiol combination on hirsutism, androgens and sex hormone binding globulin in women with a polycystic ovary syndrome.

Twenty women suffering from a polycystic ovary syndrome (PCO) accompanied by hirsutism were given a low-dose oral contraceptive combination containing 0.150 mg desogestrel plus 0.030 mg ethinylestradiol for 8 months. The pretreatment situation regarding hair and hormone profiles in the PCO group was compared with that in 22 regularly menstruating women. Serum levels of free and total testosterone and androstenedione were significantly elevated in PCO women, as were body weight, blood pressure, hair diameter and depilation frequency. Sex hormone binding globulin (SHBG) binding capacity was lower. Following treatment of the PCO group for 8 months, total and free testosterone levels were depressed, but androstenedione had not changed significantly. SHBG binding capacity was increased five-fold. Body weight decreased in the obese women. Hair growth was significantly suppressed and the hair itself was less coarse. Depilation intervals were longer. Acne, present before the treatment had now disappeared. Blood pressure did not change. Few and mild side effects were recorded. After treatment, 3 women succeeded in becoming pregnant and in 8 others spontaneous menstruations had recurred.

Adult

Lipid metabolic studies in women with a polycystic ovary syndrome during treatment with a low-dose desogestrel-ethinylestradiol combination.

Twenty women with the polycystic ovary syndrome (PCO) were treated with a combination of desogestrel and ethinylestradiol (EE) and the effects on lipids and lipoproteins were compared with those induced in a group of 13 regularly menstruating, healthy women. All women were examined before and after 3 months of treatment. Compared with the regularly menstruating women, the PCO women had significantly higher body weights and blood pressure as well as elevated levels of triglycerides in serum and VLDL. During treatment, 14 out of 20 women affected by PCO lost weight. No significant change in blood pressure was observed. In the PCO group, moderate increments were encountered in serum cholesterol, phospholipids and triglycerides. No significant changes were seen in LDL-cholesterol or HDL-cholesterol. The ratio LDL-cholesterol/HDL-cholesterol did not alter. The level of total cholesterol in VLDL rose during treatment. These changes in serum and lipoprotein lipids in PCO patients were of the same type and magnitude as those found in the control group, apart from an increase in HDL-cholesterol in the latter. The only remaining difference after treatment was a slightly higher level of VLDL triglycerides in the PCO women. Thus only moderate changes were induced in lipid and lipoprotein patterns by the combination of desogestrel and EE. A "positive" influence on lipids and lipoproteins cannot be considered as a further advantage, added to the list of indications when hormonal treatment is used in PCO-affected women. The clinical implications of elevated triglycerides remain to be clarified.

Adult

Pharmacodynamic studies on desogestrel administered alone and in combination with ethinylestradiol.

Most progestogens in oral contraceptives are testosterone derivatives and have androgenic side effects such as weight increase, acne and hirsutism. They pose a problem to many women just like the clinical picture of the polycystic ovary syndrome (PCO) with obesity, hirsutism, acne and amenorrhea. The aim of this study was to evaluate androgenicity of the most used progestogens with special reference to desogestrel which is a new progestogen. Radioimmunoassay was used for hormone determination while serum proteins were determined with electroimmunoassay or in some studies for sex hormone binding globulin (SHBG) with capacity assays. Serum lipids and lipoproteins were determined in serum and after ultracentrifugation in HDL, LDL and VLDL fractions. In a comparative study on levonorgestrel/ethinylestradiol (EE) (n = 10) versus desogestrel/ethinylestradiol (n = 10) the latter combination gave increases in SHBG capacity while the former did not. Similar increases in estrogen-sensitive proteins cortisol binding globulin (CBG) and ceruloplasmin indicated that the estrogenicity and "antiestrogenicity" was the same for the two combinations whereas the androgenicity of levonorgestrel was greater giving a reduction in the EE-induced increase in SHBG (SHBG is increased by estrogens and suppressed by androgens). When giving desogestrel 0.125-0.500 mg and lynestrenol 5 mg alone in daily doses to a group of regularly menstruating women (n = 8) strong suppression of SHBG was achieved while ceruloplasmin, CBG and thyroxine binding globulin (TBG) did not change. TBG is decreased and prealbumin increased by androgenic/anabolic activity but only a moderate increase in prealbumin was found during lynestrenol treatment. The changes in SHBG are probably the result of a dose-dependent receptor interaction related to 17 alpha-alkylation in 19-norsteroids. Twenty women with PCO were treated for 8 months with 0.150 mg desogestrel/0.030 mg EE. Evaluation was done before treatment and after 3 and 8 "pill" cycles regarding androgens, estradiol, SHBG, hirsutism and body weight. Spontaneous menstrual cycles were assessed after treatment. Serum lipids and lipoproteins were studied before treatment and at the end of the third "cycle". In PCO the suppression of increased total and free testosterone levels (in comparison to 22 healthy women) was evident during treatment, concordant with increases in SHBG capacity. Hirsutism was suppressed and body weight was reduced in obese women.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent

Androgenic, anabolic, estrogenic and antiestrogenic effects of desogestrel and lynestrenol: effects on serum proteins and vaginal cytology.

Eight healthy (apart from pelvic endometriosis) women were given daily doses of 0.125, 0.250 and 0.500 mg of desogestrel or 5 mg of lynestrenol orally in a randomized order. Duration of each treatment was 6 weeks. Serum was analyzed for sex hormone binding globulin (SHBG), ceruloplasmin, cortisol binding globulin (CBG), thyroxine binding globulin (TBG) and prealbumin using an electroimmunoassay. Serum 17 beta-estradiol (E2) and testosterone (T) were analyzed by radioimmunoassay. Vaginal cytology was studied using the maturation value (MV). E2 levels were depressed by desogestrel and lynestrenol apart from values in two women after 0.125 mg desogestrel. T concentration was suppressed by desogestrel but not by lynestrenol. SHBG concentration and MV were dose-dependently suppressed indicating an antiestrogenic or possibly androgenic effect of desogestrel and lynestrenol. No androgenic or anabolic effects of desogestrel were however seen, e.g. suppression of TBG content or increase in prealbumin levels. For lynestrenol, however, a small but significant increase in prealbumin concentration indicated a weak androgenic/anabolic effect. No estrogenic effects were seen, e.g. increases in ceruloplasmin, CBG levels or in elevations of MV. A depressed SHBG production ability in the hepatocytes during treatment with 19-nortestosterone derivatives is postulated, possibly due to competitive receptor binding.

Adult

A new combination of conjugated equine oestrogens and medroxyprogesterone for treatment of climacteric complaints.

Thirty-four post-menopausal women with climacteric complaints were given conjugated equine oestrogens (1.25 mg/day) for 21 days followed by 2 days without hormones and then 5 mg medroxyprogesteroneacetate daily for 5 days. The present trial was designed to study effects on vasomotor symptoms, bleeding patterns and endometrial histopathology. Vasomotor disturbances were completely relieved. No recurrence of symptoms was recorded in the oestrogen-free week. Withdrawal bleedings were regular and slight, which was a positive experience for those women who had previously been treated with other oestrogen-progestogen regimens. In most patients inactive or weak secretory endometrial epithelium was found during treatment. Two women developed differing degrees of hyperplasia after 2.5 and 3 yr, respectively. This fact emphasizes the necessity of adding progestogens for at least 10 days each month even if the oestrogens and progestogens are administered separately. It may also be wise to perform an endometrial biopsy when sex hormones are administered on a long-term basis.

Biopsy

Lipid metabolism in women with polycystic ovary syndrome: possible implications for an increased risk of coronary heart disease.

This study reports values of serum lipids, lipoproteins, and the relative fatty acid composition of lecithin and cholesterol ester in 20 women with typical polycystic ovary syndrome (PCO). These values were compared with values of 22 regularly menstruating women without clinical evidence of androgen excess. Higher levels of triglycerides in serum (P less than 0.05) and very low-density lipoproteins (P less than 0.01) and lower concentrations of free cholesterol in low-density lipoproteins (P less than 0.05) were found in the PCO women. In serum lecithin the PCO patients had higher palmitic and lower stearic acid levels compared with those of the normal women. This finding was interpreted as a reduction of the excretory capacity of the liver in the PCO group. No correlations between lipids and sex hormones were found. Body weights and blood pressures were higher in the PCO group. The results indicate that PCO women could be at increased risk for coronary heart disease, because an increased serum triglyceride level, body weight, and blood pressure are considered to be risk factors of coronary heart disease.

Adult

A continuous estrogen-progestogen regimen for climacteric complaints. Effects on lipid and lipoprotein metabolism.

The lipid composition of serum and the lipoprotein fractions, very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) were determined in 26 peri- and postmenopausal women treated with a daily dose of 2 mg 17-beta-estradiol, 1 mg estriol and 1 mg norethisteroneacetate in a continuous regimen for 12 months. A decrease was noted in all serum lipids, triglycerides, cholesterol and phospholipids during treatment. When comparing the lipid values after 3 and 12 months of treatment a tendency was found to approach pretreatment values with time. A reduction of triglycerides in VLDL after 3 months, concomitant with a decrease in HDL-cholesterol, was interpreted as an effect mainly of the progestogen component. A decrease of free cholesterol in LDL was found during treatment. The ratio of LDL-cholesterol/HDL-cholesterol was unaltered when comparing values before vs. after 3 and 12 months of treatment. Decreased levels of HDL-cholesterol and elevated levels of LDL-cholesterol are considered to be risk factors for coronary heart disease. The significance of lipid metabolic effects induced by treatment in the present study on a longterm basis is hard to evaluate in terms of atherogenicity.

Adult

Ethinylestradiol administered by oral and sublingual routes: a comparative study in ovariectomized women.

Eight ovariectomized women with an intact uterus received 12.5 micrograms ethinylestradiol for 14 days, in a cross over fashion. Ethinylestradiol was administered as a paper disc for sublingual application or as a tablet for oral administration. The parameters studied were FSH secretion, plasma protein synthesis, endometrial morphology, cervical mucus properties and the karyopyknotic index. Both types of treatment resulted in estrogenic effects with a more pronounced effect on sperm penetration and the Spinnbarkeit test after paper disc treatment than after conventional tablet treatment. The post-treatment FSH concentration 20 h after ethinylestradiol administration was significantly lower than the pretreatment value only in the case of the paper disc treatment. There was no evidence of any difference in effects on protein synthesis. The results indicate that the availability of ethinylestradiol for peripheral tissues may be increased by sublingual administration compared to oral tablet administration, whereas the effects on liver protein synthesis may remain unchanged.

Administration, Oral

Vaginal absorption of two estriol preparations. A comparative study in postmenopausal women.

In a comparative randomized cross-over study the absorption of a single dose of 0.5 mg estriol from a vaginal cream or a vaginal suppository (OvestinR, Organon, The Netherlands) was studied. Eight healthy postmenopausal women participated and the preparations were given with an interval of 14 days. Blood sampling was performed twice before application and then after 1/4, 1/2, 1, 2, 4, 6, 8, 24 and 48 hours. Serum was analysed for unconjugated and conjugated estriol (E3), FSH and LH by radio-immunoassay. Considerable interindividual variations in serum levels of unconjugated E3 were found but mean values were about equal throughout the study for the two preparations. Peak levels of 0.5-0.6 nmol/l were achieved 1-2 hours after application of the preparations and after 24 hours no unconjugated E3 was measurable. Conjugated E3 rose rapidly but within 48 hours serum concentrations reached baseline levels. A maximum decrease in serum LH levels of about 40% was obtained with both preparations after 6 hours and the return to baseline within 24 hours indicates a relationship to unconjugated E3. FSH in serum was maximally suppressed 6-12%. Estriol is thus readily absorbed by the vaginal route and peak levels of unconjugated E3 after insertion of 0.5 mg estriol seem to be comparable to those obtained after 8-12 mg estriol given orally.

Absorption