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Biomedical subjects

G Silfverstolpe

Publications and source records attributed to G Silfverstolpe.

At least 37 records · Page 2Linked to original sources

Fatty acid composition of serum lecithin and cholesterol ester in the normal menstrual cycle.

Gonadal hormones and the relative fatty acid composition of serum lecithin and cholesterol ester were studied on four occasions during one cycle in twenty-two regularly menstruating women. The most evident change during the menstrual cycle was a decrease in the sum of polyunsaturated fatty acids of the linoleic series in the late luteal phase. Concomitantly an increase in oleic acid as well as palmitic acid was recorded. These changes were considered to be dietary influenced since a shift of the oleic/linoleic acid ratio is often seen when fat is replaced by sugar and some women are known to increase their intake of refined carbohydrates premenstrually. The only correlation found for fatty acids and hormone levels was a correlation of the ratio oleic/linoleic acids and 17-beta-estradiol. This pattern is not seen after administration of exogenous estrogens and obviously there is a discrepancy between endogenous and exogenous estrogens in this context. Whether physiological fluctuations of sex hormones during the menstrual cycle directly influence the fatty acid composition of serum lecithin and cholesterol ester is uncertain. No changes in dihomo-gamma-linolenic acid or arachidonic acid, the major precursors of prostaglandin synthesis were recorded.

Adolescent↗

Changes in relative fatty acid composition of serum lecithin and cholesterol ester after treatment with two gonane progestins administered alone and in combination with ethinyl estradiol.

Twenty women, oophorectomized as part of treatment for cervical carcinoma of the cervix participated in the study. Ten of them were given desogestrel (DG) 150 micrograms/day for 3 weeks followed by DG + 30 micrograms ethinyl estradiol (EE) for 6 weeks, and finally EE alone for 3 weeks. The other 10 women were given 150 micrograms levonorgestrel (NORG) and EE in a similar way. Before treatment and after each period of treatment the relative fatty acid composition of serum lecithin and serum cholesterol ester were assessed by gas-liquid chromatography. In both groups ethinyl estradiol, when administered alone, increased arachidonic acid in serum lecithin. This increase was not observed on the DG + EE or the NORG + EE combination indicating that both progestins counteracted this estrogenic effect.

Adult↗

Lipid composition of serum lipoproteins in relation to gonadal hormones during the normal menstrual cycle.

Twenty-two normally menstruating women were studied during one menstrual cycle. Blood was collected on 4 occasions and was analysed for free and total cholesterol and triglycerides and phospholipids in the lipoprotein fractions, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Fluctuations in lipid parameters were correlated to serum levels of estradiol-17 beta, progesterone, androstenedione, testosterone and sex-hormone-binding globulin (SHBG). Elevated concentrations of SHBG and HDL-cholesterol and a suppression of LDL-cholesterol were found during the luteal compared to the follicular phase and these findings were interpreted as an estrogenic influence. Consequently the ratio LDL-cholesterol/HDL-cholesterol was depressed during the luteal phase. Triglycerides in serum and VLDL reached a peak at midcycle. When effects on lipid metabolism induced by endogenous steroids were compared to lipoprotein fluctuations exerted by exogenous hormones a parallelism was found in certain variables. However, obvious discrepancies were also found in effects on lipid metabolism, especially for hormones with androgenic properties. The present data underline the necessity of defining in which menstrual phase blood has been collected when lipid metabolism is studied in women of fertile age. Knowledge about metabolic events induced by exogenous sex steroids does not allow conclusions concerning the effects exerted by corresponding endogenous hormones.

Adolescent↗

Apolipoprotein A1 levels in oophorectomized women treated with Org OD 14, oestradiol valerate and a placebo.

Org OD 14 is a synthetic steroid which in animal bioassays displays oestrogenic as well as very weak androgenic-anabolic properties. Earlier studies have shown that it alleviates oestrogen-deficiency symptoms and retards osteoporosis. OD 14 can be administered continuously with little effect on the endometrium. The aim of this study was to evaluate the effect of OD 14 on apolipoprotein A1 (Apo-A1), the major protein constituent of the high-density lipoprotein (HDL) fraction, as compared with that of oestradiol valerate (E2V) and a placebo. Twenty-two women, who had been oophorectomized when undergoing surgical treatment for stage IB or IIA cervical carcinoma, were given OD 14 2.5 mg/day, a placebo, and E2V 2 mg/day for a period of 6 wk in each case using a double-blind, cross-over method. Serum Apo-A1 was determined by electro-immunoassay after each treatment period. There was a marked decrease in Apo-A1 after OD 14 as compared with the levels seen after the placebo and E2V. This decrease is interpreted as evidence of a strong androgenic influence by OD 14. In epidemiological studies low levels of Apo-A1 have been associated with a higher incidence of atherosclerosis and cardiovascular disease. Long-term treatment with OD 14 might therefore be hazardous in this respect.

Adult↗

Changes in serum apo-lipoprotein AI and sex-hormone-binding globulin levels after treatment with two different progestins administered alone and in combination with ethinyl estradiol.

Twenty women, oophorectomized as part of the surgical treatment for cervical carcinoma in either clinical stage IB or IIA but otherwise healthy, participated in the study. After a period of six weeks without hormonal treatment, ten of them were given 150 micrograms desogestrel (DG) daily for three weeks followed by 150 micrograms DG + 30 micrograms ethinyl estradiol (EE) for six weeks and, finally, 30 micrograms EE alone for three weeks. The remaining ten women were given 150 micrograms levonorgestrel (NORG) and EE in a similar regimen. Before treatment and after each period of treatment, apo-lipoprotein AI and sex-hormone-binding globulin (SHBG) were assayed in serum. Both progestins decreased apo-AI and SHBG when given alone, thereby indicating an "androgenic" influence. In combination with EE, however, DG seems to be less "anti-oestrogenic" than NORG, as judged from the higher apo-AI and SHBG values after the combination DG + EE compared to those after NORG + EE.

Adult↗

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↗

Changes in apolipoprotein AI after treatment with high-dose medroxyprogesterone acetate.

21 women (mean age 60 years, range 48-72) were given depot medroxyprogesterone acetate (DMPA), 1,000 mg/week parenterally for 6 months, as part of the treatment for endometrial carcinoma in either clinical stage I or II. Before treatment and after 1, 3 and 6 months of treatment serum apolipoprotein AI was analyzed by electroimmunoassay. There was a significant decrease in apolipoprotein AI after the administration of DMPA, compared to the value before treatment. A low level of apolipoprotein AI is considered a risk factor for the development of atherosclerosis and cardiovascular disease. Such a risk might therefore be anticipated if the period of treatment was extended to several years.

Aged↗

High-dose depot-medroxyprogesterone acetate (DMPA) - effects on lipid and lipoprotein metabolism.

Twenty-one women were given depot-medroxyprogesterone acetate (DMPA) 1000 mg/wk for 6 mth as part of the treatment for endometrial carcinoma in either clinical stage I or II. Total and free cholesterol, triglycerides and phospholipids were analysed in serum and in the ultracentrifugally separated lipoprotein fractions VLDL, LDL and HDL (very low, low and high density lipoproteins). Previous studies have shown little effect on lipoprotein metabolism after lower doses of MPA, unlike progestins of the 19-nor-testosterone series, after which an 'androgenic' lipoprotein pattern is seen, i.e., a decrease in HDL-cholesterol and in triglycerides in serum and VLDL. After this massive DMPA dose, only a slight decrease in HDL-cholesterol was seen, as well as a rise in triglycerides in serum and VLDL. We interpret the latter finding as secondary to an influence on carbohydrate metabolism.

Aged↗

Oral contraception with a nonalkylated estrogen component. Effects on lipid metabolism.

All commercially available combined oral contraceptives have 17-C-alkylated estrogens (ethinylestradiol or mestranol) as their estrogen components. In postmenopausal replacement therapy nonalkylated 'natural' estrogens have been shown to induce less adverse effects in lipid metabolism than alkylated estrogens. To see if this difference is valid also when the respective kinds of estrogens are used as components in oral contraceptives, the lipid metabolic effects from two preparations with the same progestogen component (norethisterone acetate) but with nonalkylated (17 beta-estradiol; Netagen) and alkylated (ethinylestradiol) estrogen (Netasyn) have been evaluated. Phospholipids, cholesterol, and triglycerides have been assessed in serum and in ultracentrifugally isolated lipoprotein fractions. The serum lecithin fatty acid composition has been analysed by gas-liquid chromatography. Netasyn increased the triglyceride content of serum and all lipoprotein fractions while Netagen did not. Netasyn caused a redistribution in the 1-position fatty acids of serum lecithin with an increase in palmitic and a concomitant decrease in stearic acid, a pattern associated with the 17-C-alkylation of a steroid and probably its capacity to inhibit liver excretory function. In the present study the preparation with the non-alkylated estrogen component had less adverse lipid metabolic effects than the conventional oral contraceptive.

Contraceptives, Oral↗

A double blind cross-over study on the effects of ORG OD14 compared to estradiol valerate and placebo on the fatty acid composition of serum lecithin and cholesterol ester in oophorectomized women.

Twenty-two women, oophorectomized in connection with surgical treatment for cervical carcinoma in clinical stage IB or IIA, were given ORG OD14 [(7 alpha,17 alpha)17-hydroxy-7-methyl-19-norpregn-5-(10)20-yn-3-one; 2.5 mg/day], a placebo, and estradiol valerate (2 mg/day), six weeks each, in a double blind, cross-over study. ORG OD14 is a synthetic steroid for continuous treatment of climacteric symptoms which in traditional bioassays has been shown to have weak estrogenic and progestogenic as well as very weak androgenic-anabolic properties. The aim of this study was to evaluate its effects on serum lecithin as well as on the relative fatty acid composition of serum lecithin and serum cholesterol ester. In serum lecithin, OD14 induced an increase in palmitic acid and a decrease in stearic acid, effects typical of 17-C-alkylated steroids, compared to both placebo and estradiol valerate. Furthermore, there was an increase in linoleic acid and a decrease in both arachidonic and dihomo-gamma-linolenic acid after OD14 administration. This decrease is interpreted as an inhibitory action of the steroid on the mechanisms of elongation and desaturation of linoleic acid and is considered to be an androgenic influence. The relative decrease is further accentuated by the decrease in total serum lecithin induced by OD14. Since these fatty acids are the major precursors for prostaglandin synthesis, these findings might have relevance in that context.

Adult↗

A double-blind cross-over study on the effects of ORG OD14 compared to oestradiol valerate and placebo on lipid and carbohydrate metabolism in oophorectomized women.

ORG OD14 is a synthetic steroid which in traditional bioassays has been shown to have oestrogenic and progestogenic as well as very weak androgenic-anabolic properties. As judged from earlier studies, this steroid seems suitable for continuous treatment of climacteric deficiency symptoms. The aim of this study was to evaluate the effects induced by OD14 on lipid, lipoprotein and carbohydrate metabolism, as compared to E2V and placebo. Twenty-two women, oophorectomized as part of the treatment of cervical carcinoma in clinical stage IB or IIA, were given ORG OD14 2.5 mg/day, oestradiol valerate (E2V) 2 mg/day and a placebo for 6 weeks each, in a double-blind cross-over study. There was a marked decrease in all lipid components of HDL (high density lipoprotein), i.e. total and free cholesterol, triglycerides and phospholipids (P less than 0.001), after OD14. The oral glucose tolerance test showed higher values after OD14 compared to both E2V and placebo (P less than 0.05), indicating a slightly impaired glucose tolerance. The lipid metabolic changes induced by OD14 indicate a rather strong androgenic influence in this respect.

Adult↗

Lipid and carbohydrate metabolism studies in oophorectomized women: effects produced by the addition of norethisterone acetate to two estrogen preparations.

Norethisterone acetate (NET) was administered to 11 oophorectomized women, primed with either 17-C-alkylated ethinylestradiol (EE) or the non-alkylated estrogen, estradiol valerate (E2V), to evaluate the effects on lipid metabolism. Blood samples were drawn after a period without hormonal replacement therapy and after 6 weeks on each estrogen and estrogen-progestogen combination. Serum and lipoprotein lipids were followed and an oral glucose tolerance test was performed with blood glucose and plasma insulin determinations. NET reversed the increase in serum triglycerides induced by EE and, when added to either estrogen, increased low density lipoproteins and reversed the high density lipoprotein lipid increase induced by both estrogens. The NET + EE, but not the NET + E2V combination, imparied glucose tolerance.

Adult↗

Lipid metabolic studies in oophorectomised women: effects on serum lipids and lipoproteins of three synthetic progestogens.

Norethisterone acetate, medroxyprogesterone acetate and levonorgestrel were administered to oophorectomised women to evaluate the effects they have on lipid metabolism. Blood samples were drawn after a 3 wk period without hormone therapy and after 3 wk on each progestogen. Serum and lipoprotein lipids were followed and an oral glucose tolerance test with blood glucose and plasma insulin determinations were performed. The nortestosterone derivatives, norethisterone acetate and levonorgestrel, decreased high density lipoprotein cholesterol as well as alpha-lipoproteincholesterol, while the 17-hydroxyprogesterone derivative medroxyprogesterone acetate did not. Norethisterone acetate and medroxyprogesterone acetate impaired glucose tolerance. A difference between nortestosterone derivatives and 17-hydroxyprogesterone derivatives having an effect on high density lipoproteins is suggested.

Adult↗

Lipid metabolic studies in oophorectomized women: effects of synthetic progestogens on individual serum phospholipids and serum lecithin fatty acid composition.

Norethisterone acetate (NET), levonorgestrel (NORG) and medroxyprogesterone acetate (MPA) were administered to oophorectomized women to evaluate the effects on individual serum phospholipids as well as serum lecithin and cholesterol ester fatty acid composition. Blood samples were drawn after a 3-week period without hormonal replacement therapy and after 3 weeks on each progestogen. NORG reduced cepahlin and lecithin with a concomitant increase in lysolecithin. This shift in individual phospholipids has previously been induced by exogenous androgens. The 17C-alkylated synthetic progestogens NET and NORG but not the non-alkylated MPA caused a redistribution among the 1-position fatty acids of serum lecithin with an increase in palmitic concomitant with a decrease in stearic acid. These findings indicate differences between 19-nortestosterone derivatives and 17-hydroxyprogesterone derivatives in effect on individual serum phospholipids and in influence on liver lecithin synthesis as judged from serum lecithin fatty acid composition.

Adult↗

Does progestogen reduction in oral contraception parallel reduced lipid metabolic effects?

Twelve young fertile women participated in a cross-over design study whose purpose was to evaluate the effect on lipid metabolism induced by two sequential contraceptive preparations. Sequilarum (50 micrograms of ethinylestradiol + levonorgestrel where the levonorgestrel dose is varied from 50 micrograms during the first 11 days up to 125 micrograms during the lst 10 days of the cycle) was compared with Ovanone (50 micrograms of ethinylestradiol for 22 days with the addition of 2.5 mg lynestrenol during the last 15 days of the cycle). Serum triglycerides, phospholipids, free and total cholesterol were determined, and also was the level of these lipid components in ultracentrifugally isolated lipoprotein lipids. The relative fatty acid composition of serum lecithin and serum cholesterol ester was assessed by gas-liquid chromatography. As expected, both of these preparations are predominantly estrogenic in their effects on lipoprotein metabolism, since both raise serum and VLDL triglyceride levels. The absence of any substantial influence on HDL cholesterol should probably be interpreted as a modifying effect of the progestogen component of both preparations. As to the relative fatty acid composition of serum lecithin the shift induced in palmitic and stearic acids was the same as found in earlier studies when 17C-alkylated exogenous sex steroids were administered, i.e. an increase in the palmitic acid concomitant with a decrease in the stearic.

Adolescent↗

Effects induced by two different estrogens on serum individual phospholipids and serum lecithin fatty acid composition.

Eleven oophorectomized women (mean age 34.5 +/- 5.9) received two treatment cycles, one of the 17-C-alkylated ethinyl estradiol 20 microgram per day, and the second of the non-alkylated estrogen, estradiol valerate 2 mg per day for six weeks in separate periods preceded by six weeks without hormonal replacement therapy. Blood samples were drawn before and after six weeks on each estrogen. The samples were assayed for individual phospholipids i.e. cephalin, lecithin, lysolecithin and sphingomyelin after separation of these lipids by thin layer chromatography. The relative fatty acid composition of serum and high density lipoprotein lecithin and serum cholesterol ester was determined by gas liquid chromatography. Both estrogens reversed the symptoms of estrogen deficiency and had similar effects on serum individual phospholipids i.e. causing an increase in lecithin concomitant with a decrease in lysolecithin. It is suggested that this lecithin-lysolecithin shift could depend on an inhibition of the hepatic lipase and its phospholipase A1-activity. Both estrogens increased serum lecithin arachidonic acid without causing any change in linoleic acid (the major essential fatty acid), which indicates that this increase in arachidonic acid could be an estrogenic effect independent of dietary factors. Ethinyl estradiol caused an increase in palmitic and a decrease in stearic acid in the 1-position of serum lecithin while estradiol valerate did not influence these fatty acids at all. This palmitic-stearic acid shift induced by ethinyl estradiol is interpreted as a non-hormonal "drug-effect" linked to the liver toxicity of 17-C-alkylated steroids in spite of the lack of influence on routine liver function tests.

Adult↗