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Biomedical subjects

G Silfverstolpe

Publications and source records attributed to G Silfverstolpe.

At least 19 recordsLinked to original sources

The effects of transdermal estradiol and oral conjugated estrogens on haemostasis variables.

The effects of oral and transdermal administration of estrogen replacement therapy (ERT) have been fairly well investigated regarding lipoprotein and carbohydrate metabolism, while the effects of different modes of estrogen administration on the haemostatic system have been less well studied. To delineate and compare the effects of perorally administered conjugated estrogens (CE) and transdermally administered estradiol (E2) in doses needed for hormone replacement therapy (HRT) on haemostasis parameters, 23 postmenopausal women were engaged in a study with an open cross-over design. The doses compared (0.625 mg CE and 50 micrograms E2/24h) are the lowest which, with few exceptions, eliminate climacteric symptoms. Both CE and E2 increased factor VII:C, factor VII:Ag, and the prothrombin fragment1 + 2. The increase in factor VII:Ag, however, was significantly higher after treatment with CE. These changes were all towards a state of hypercoagulability. Furthermore, CE decreased plasminogen activator inhibitor (PAI) and the thrombin-antithrombin complexes (TAT), as well as antithrombin (ATIII).

Administration, Cutaneous↗

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↗

Effects of early pregnancy on regional adipose tissue metabolism.

Adipose tissue metabolism was studied in needle biopsies from femoral and abdominal subcutaneous depots, in 12 healthy young women, during early (9-11 weeks) pregnancy, and 6 weeks after a legal abortion. Both during pregnant and non-pregnant conditions, a higher lipoprotein lipase (LPL) activity was seen in the femoral compared to the abdominal region, but the LPL activity was not influenced by early pregnancy. Rates of fatty acid esterification and acylglyceride synthesis were not different between regions, nor affected by pregnancy. The stimulatory effect of norepinephrine (10(-7) M) on lipolysis was significantly greater in the abdominal than in the femoral region in both the pregnant and non-pregnant condition. This difference was apparently due to higher alpha-adrenergic activity in the femoral region. Pregnancy per se had no effect on lipolytic response to norepinephrine. These findings indicate that lipid accumulation is favoured in the femoral region in young women both during pregnant and non-pregnant conditions.

Abdomen↗

Regional adipose tissue metabolism in postmenopausal women after treatment with exogenous sex steroids.

In order to evaluate the effect of exogenous sex steroids on adipose tissue metabolism, two groups of postmenopausal women were studied. In one of the groups, the effect of 50 micrograms ethinyl estradiol (EE) was investigated given orally alone and in combination with 10 mg norethisterone acetate (NET). This combination is reminiscent of an old high dose oral contraceptive. In the other group, the effect of 3 mg 17 beta-estradiol was evaluated when administered percutaneously alone and in combination with 300 mg micronized progesterone given orally. These substances and doses were chosen to provide a "physiological" hormonal influence. In the femoral region 50 micrograms EE induced an increase in LPL activity. This elevated LPL value was reversed with the addition of 10 mg NET. Moreover, during treatment with 50 micrograms EE, a decrease in norepinephrine stimulated lipolysis was seen in the abdominal region. The percutaneous administration of 17 beta-estradiol with or without micronized progesterone, however, was inert as regards subcutaneous adipose tissue metabolism. Our findings indicate, therefore, that EE in doses used in oral contraception might promote lipid accumulation in the femoral adipose tissue depot.

Adipose Tissue↗

A comparison between effects of estradiol valerate and low dose ethinyl estradiol on haemostasis parameters.

Ethinyl estradiol (EE) is still used to some extent as hormonal replacement therapy (HRT) in the climacteric period. As regards oral contraception, it is well known that the induced increase in cardiovascular disease is related to the estrogen component (invariably EE) in a dose-related fashion. Considerably lower doses of EE are needed in HRT compared to oral contraception. To delineate and compare effects of EE and estradiol valerate (E2V) in doses needed in HRT on haemostasis parameters, 24 postmenopausal women were engaged in a study with an open cross-over design. The doses compared (10 micrograms EE and 2 mg E2V daily) are the lowest which eliminate climacteric symptoms in a majority of women. Unlike E2V, EE caused increased levels of factor VII:Ag, factor VIII:C and beta-thromboglobulin, which may be changes towards hypercoagulability. Both estrogens decreased the AT III activity. Long-term administration (6 + 12 w) of the estrogens induced further changes in haemostatic parameters. 10 micrograms EE increased factor VII:Ag in contrast to 2 mg E2V. Furthermore both estrogens increased factor VIII:C and factor II-VII-X. A decrease in platelet count was induced by both EE and E2V. Oral contraception and adjuvant estrogen therapy in men with prostatic carcinoma are known to imply an increased cardiovascular risk. It is noteworthy that the pattern of changes in haemostatic parameters induced by as little as 10 micrograms of EE is the same as seen after the administration of combined oral contraceptives or the substantially higher doses of EE given as adjuvant therapy to men with prostatic carcinoma.

Adult↗

A comparison of the effects of ethinyl estradiol and estradiol valerate on serum and lipoprotein lipids.

Serum lipids and lipoproteins were assessed after treatment with 2 mg of oestradiol valerate (E2V) and 10 micrograms of ethinyl oestreadiol (EE) in a group of 24 oophorectomised women in a study with an open cross-over design. E2V in this oral dose was quite inert in its effect on lipoprotein lipids. Ten micrograms of EE is a dose which in most women is sufficient to alleviate post-menopausal vasomotor symptoms. However, this low dose of EE increased serum triglycerides as a result of increased levels in the ultracentrifugally isolated lipoprotein fractions. Increased levels of serum and lipoprotein triglycerides are considered cardiovascular risk factors in women.

Adult↗

Treatment of climacteric complaints with Org OD 14: a comparative study with oestradiol valerate and placebo.

Org OD 14 (7 alpha,17 alpha-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one) is a steroid possessing mixed hormonal activity, which in earlier studies has been shown to alleviate climacteric complaints and to prevent post-menopausal osteoporosis without affecting the endometrium. The effects of Org OD 14 on climacteric complaints were compared with those of oestradiol valerate (E2V) and placebo in a randomized, double-blind, cross-over study in 20 women who had been oophorectomized and hysterectomized 3-6 yr earlier as part of their treatment for cervical cancer. Each patient was treated orally for a total period of 18 wk, comprising 6 wk on each preparation. Capsules of identical appearance were given; these contained either 2.5 mg Org OD 14, 2 mg E2V or placebo. The patients' scores for symptoms and mood items on standardized rating scales were recorded at the end of each 6-wk treatment period (i.e. on days 43, 85 and 127). There were no differences between the effects of Org OD 14 and E2V on symptoms and mood items, while both compounds were more effective than placebo. Our findings confirmed that Org OD 14 is effective in ameliorating oestrogen deficiency symptoms in climacteric women.

Adult↗

Dose and duration effects of oestradiol valerate on serum apolipoproteins A1 and B.

The serum levels of apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) were assessed by electroimmunoassay in 19 bilaterally oophorectomised women before and after treatment with 2 and 4 mg oestradiol valerate (E2V) daily. The first part of the study was conducted in accordance with an open cross-over design. The levels of ApoA1 were found to have increased after the 6-week treatment periods using each of those dosages, the increase being most pronounced after treatment with 4 mg E2V. ApoB concentrations decreased at both dosage levels. The serum levels of total (TC) and free cholesterol (FC) and phospholipids (PL) in the high-density lipoprotein (HDL) fraction correlated positively with the serum levels of ApoA1 before treatment. The correlations between serum ApoA1 and HDL-PL levels persisted after both dosage regimens. Before and after treatment with 2 mg E2V, serum ApoB levels correlated positively with the levels of all lipid components in the low-density lipoprotein (LDL) fraction. After 4 mg E2V, serum ApoB levels correlated positively with LDL-PL and LDL-TC levels. On conclusion of the cross-over, in order to assess the effects of the duration of therapy, the women were followed up for a further period of 3 mth, during which ten were given 2 mg and the other nine 4 mg of E2V daily. The increased levels of ApoA1 and the decreased levels of ApoB seen after the cross-over study were not found to have altered after this treatment-duration evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of cyproterone acetate (CPA) on serum lipoproteins when administered alone and in combination with ethinyl estradiol (EE).

The effects of serum lipids and lipoproteins of 2 mg cyproterone acetate (CPA) given alone and in combination with 35 or 50 micrograms ethinyl estradiol (EE) were studied in 21 oophorectomized women in a study with a cross-over design. CPA in this low oral dose was rather inert in its effects on lipoprotein lipids. It induced only a small decrease in the free cholesterol and phospholipid content of the high density lipoprotein (HDL) fraction. As regards the CPA-EE combinations, they induced a slight increase in the HDL fraction, a small decrease in the low density lipoprotein (LDL) fraction and a substantial increase in triglycerides both in the serum and in the very low density lipoprotein (VLDL) fraction. This lipoprotein pattern is invariably induced after the administration of an alkylated estrogen or an "estrogen dominated" oral contraceptive. An increase in triglycerides is a "biochemical" adverse effect which may have clinical implications for some patients.

Adult↗

Dose and duration effects of estradiol valerate on serum and lipoprotein lipids.

Non-alkylated estrogens, like estradiol valerate (F2V), are widely used in the treatment of the postmenopausal hormonal deficiency syndrome. Their effects on serum and lipoprotein lipids are characterized by an increase in the lipid constituents of high density lipoproteins (HDL) and, usually, a decrease in low density lipoproteins (LDL). These effects are considered beneficial as regards atherogenesis and the risk for cardiovascular diseases. Unlike the effects of alkylated estrogens, no concomitant increase in triglycerides (TG) in serum and very low density lipoproteins (VLDL) - adverse effects - are seen in doses of up to 2 mg E2V. In order to compare the effects of 2 and 4 mg of E2V on serum and lipoprotein lipids, 19 bilaterally oophorectomized women participated in a cross-over study after a 4 week long wash-out period. To evaluate the influence of the time factor, 10 of the women continued taking 2 mg and 9 taking 4 mg of E2V respectively for an additional period of 12 weeks, resulting in a total treatment period of 24 weeks per group. The serum lipoproteins were separated by preparative ultracentrifugation, the serum and lipoprotein lipids being assessed using commercially available kits. In the cross-over part of the study, total (TC) and free cholesterol (FC) and phospholipids (PL) increased in HDL and decreased in LDL. Neither dose increased TG in serum or VLDL. These changes in the lipoprotein pattern persisted at the end of the entire study. Consequently, within the range of commonly used doses (2 and 4 mg) E2V seems to have a constant and, in terms of cardiovascular disease, favourable influence on lipoprotein metabolism irrespective of doses and periods studied.

Administration, Oral↗

The effects of two gonane progestins alone and in combination with ethinyl estradiol on serum lipoproteins.

Twenty women, oophorectomized as part of the treatment for cervical carcinoma in an early stage but otherwise healthy, participated in the study. Ten of them were given desogestrel (DG) 150 micrograms/day for 3 wk followed by DG + 30 micrograms ethinyl estradiol (EE) for 6 wk, and finally EE alone for 3 wk. The other ten women were given 150 micrograms levonorgestrel (NORG) and EE in a similar way. Before treatment and after each period, total and free cholesterol (TC, FC) triglycerides (TG) and phospholipids (PL) were assayed in serum and in the ultracentrifugally isolated lipoprotein fractions very low, low and high density lipoproteins (VLDL, LDL and HDL). The results indicate that both progestins induced the same 'androgenic' pattern when given alone, i.e. a decrease in serum- and HDL-TC and a decrease in VLDL-lipids. In combination with EE, however, DG seems to counteract the effects of EE to a lesser extent than NORG, as judged particularly from the effects on TG and PL in serum and VLDL.

Adult↗

High-dose depot-medroxyprogesterone acetate--effects on the fatty acid composition of serum lecithin and cholesterol ester.

Twenty-one women were treated with high doses of depot-medroxyprogesterone acetate (1000 mg/week im) for 6 months as part of the treatment of endometrial carcinoma. The relative fatty acid composition of serum lecithin and cholesterol ester were analyzed. In previous studies low doses of medroxyprogesterone acetate (MPA), in contrast to progestins of the 19-nor-testosterone series, have been shown not to affect the fatty acid composition of serum lecithin and cholesterol ester. However, the high doses of MPA used in this study increased linoleic acid and decreased arachidonic and di-homogammalinolenic acids in serum lecithin. The ability of a steroid to induce this shift has been ascribed to its androgenicity. MPA is considered to have weak, if any, such properties. The findings of this study emphasize the necessity to delineate effects on metabolism of different doses and administrative routes of any particular steroid.

8,11,14-Eicosatrienoic Acid↗