G. Samsioe

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

Abstract. 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.

Studies in cholestasis of pregnancy. I. Clinical aspects and liver function tests.

Abstract. Fifty‐nine consecutive pregnant women complaining of pruritus without obvious dermatological cause were studied. In 57 women the presence in serum of an abnormal lipoprotein, LP‐X, characteristic conditions associated with cholestasis, was verified by an immunological technique. These 57 women were designated as having cholestasis of pregnancy. Clinical symptoms were related to liver function tests: serum bilirubin, alkaline phosphatase, SGOT and SGPT. Compared with women with uncomplicated pregnancy, these patients showed a high frequency (p<0.05) and long duration (p<0.001) of emesis, food‐ and drug idiosyncrasy (p<0.001) and gall bladder disease (p<0.05).

Estrogen-Progestogen Replacement in Climacteric Women, Particularly as Regards a New Type of Continuous Regimen

Abstract. Twenty‐six peri‐ and postmenopausal women were treated with daily dose of 2 mg 17‐β‐estradiol, 1 mg estriol and 1 mg norethisterone‐acetate in a continuous regimen for 12 months. Clinical parameters such as vasomotor symptoms, bleeding patterns and histopathology were recorded. Blood samples were collected before, after 3 months and after 12 months of treatment and were analysed for estradiol‐17‐β, estrone, androstenedione in serum and lipoprotein lipids.

Studies in Cholestasis of Pregnancy

Abstract. Eight pregnant women, complaining of generalized pruritus with lipoprotein‐X (LP‐X) in their serum and diagnosed as cases of cholestasis of pregnancy (CP)—were studied during pregnancy and after delivery. Ten women with uncomplicated normal pregnancy served as controls. LP‐X, liver function tests and relative fatty acid composition of serum lecithin (determined by gas‐liquid chromatography, GLC) were followed. the fatty acid composition in liver and serum lecithin is determined by the synthesis pathways of lecithin in the liver. the faster and quantitatively dominating cytidine‐diphosphate diglyceride pathway, pathway I, causes the appearance of lecithin with palmitic acid (16:0) in 1‐position and oleic (18:1) or linoleic (18:2) acid in 2‐position, while pathway II, with methylation of phosphatidyl‐ethanolamine (cephalin) preferentially causes the appearance of lecithin with stearic acid (18:0) in 1‐position and arachidonic acid (20:4) in 2‐position. Pathway I is enhanced by oestrogenic and pathway II by cholestatic influence. During pregnancy women with CP were characterized in their serum lecithin fatty acid composition by a high palmitic (16:0) and a high oleic (18:1) acid content, in agreement with earlier studies. After delivery, in women with prior CP a decrease in palmitic (16:0) and linoleic (18:2) acids and an increase in stearic (18:0) acid, was interpreted as decreased influence on the major lecithin synthesis pathway I and an enhancement of pathway II. in addition, after delivery in the lactating mother, serum lecithin fatty acid composition data revealed an essential fatty acid (EFA) “consumption”. It was earlier shown, that women with previous CP (when studied 8–21 months after delivery) had as judged from their serum lecithin fatty acid composition, a “basic metabolic defect”, expressing presumably an estrogen enhanced pathway II of liver lecithin synthesis. in the present study, soon after delivery (on day 4–8) women with prior CP showed, however, less pathway II influence than women with a prior normal pregnancy. This was interpreted as a persistence of the cholestatic influence on liver lecithin synthesis pathways at this short time after delivery. Serum lecithin fatty acid composition appears to be a sensitive variable for the evaluation of metabolic influences in the liver.

Studies in Normal Pregnancy: I. Serum Lipids and Fatty Acid Composition of Serum Phosphoglycerides

Abstract. Elevated serum lipids in normal pregnancy have been confirmed by the present study. In normal pregnancy the relative fatty acid composition of serum lecithin was characteristically high in palmitic acid (16:0). From the present knowledge of lipid metabolism in pregnancy there is no obvious explanation for this finding. Furthermore, the serum lecithin relative fatty acid composition mirrored a possible dietary influence with a decrease in the essential fatty acid, linoleic (18:2) and arachidonic (20:4) acids and of the sum of the fatty acid of the linoleic acid series (n‐6). This expression for a relative deficiency in essential fatty acids might be due to changes in dietary habits during pregnancy, e.g. an increase in particularly refined carbohydrates. Reciprocal changes in oleic (18:1) and linoleic (18:2) acids further support this suggestion. An expected increase in serum lecithin containing arachidonic acid (20:4)—due to estrogen influence on liver lecithin synthesis—could not be verified in week 34 of the normal pregnancy.

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

Abstract. Twenty women with the polycystic ovary syndrome (PCO) were treated with a combination of deso‐gestrel 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‐chol‐esterol/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‐af‐fected women. The clinical implications of elevated triglycerides remain to be clarified.

Study on Effect of 30 μg Ethinylestradiol (Ee)+150 μg Desogestrel on Lipid and Lipoprotein Metabolism in Healthy Volunteers, Also in Comparison with 30 μg Ee + 150 μg Levonorgestrel

Abstract. In a cross‐over design study, 15 healthy young volunteers were randomly allocated an oral contraceptive containing 30 μg EE. Preparation A contained in addition 150 μg of a new progestogenic compound, desogestrel, and preparation B 150 μg levonorgestrel. Subjective side effects were few during use of any of the preparations.

Studies in cholestasis of pregnancy. V. Gallbladder disease, liver function tests, serum lipids and fatty acid composition of serum lecithin in the non-pregnant state.

Abstract. Women from an earlier series of cholestasis of pregnancy (CP) were called for a retrospective study to consider presence of gallstones in the gallbladder (evaluated by cholecystography), liver function tests, serum lipids and lipoproteins and the relative fatty acid composition of serum lecithin (as determined by GLC). The attendance in the retrospective study was 60%. Estimated on the total series (assuming that none of the non‐responders would have a positive X‐ray), the incidence of gallbladder disease was 23.7%. Among women with previous cholestasis of pregnancy and with a positive X‐ray finding no characteristic changes in liver function tests or serum lipids were revealed. The women with positive X‐ray had, however, a lower α‐lipoprotein cholesterol than women with negative X‐ray. A characteristic finding among women with positive X‐ray was furthermore the low relative content of palmitic acid (16:0) in serum lecithin. Also women with negative X‐ray had a lower relative content of palmitic acid than controls. It is suggested that the low palmitic acid content is expressive of an influence on liver lecithin synthesis pathways and that the serum lecithin fatty acid composition reflects similar changes in bile lecithin. The “basic defect” in CP influencing liver lecithin synthesis might be the primary cause for disturbed cholesterol solubility in bile and of the frequent occurrence of gallstones in CP.

Studies in cholestasis of pregnancy. III. Fatty acid composition of serum phosphoglycerides.

Abstract. The influence of cholestasis of pregnancy (CP) on liver lipid synthesis as reflected by the composition of serum phosphoglycerides was studied in 28 pregnant women in the last trimester by means of gas‐liquid‐chromatography (GLC). All patients complained of pruritus and had immunologically detectable lipoprotein‐X (LP‐X) in serum. Twenty women with uncomplicated pregnancies served as a control series. In lecithin, low palmitic acid (16:0) and high oleic acid (18: 1 (n‐9)) were found which appear to be characteristic for CP. The increased oleic acid suggests an enhanced liver lecithin synthesis through the cytidine‐diphosphate di‐glyceride pathway. Measurement of the concentrations of lecithin from the gas‐liquid‐chromatograms was made possible by the use of an internal standard fatty acid added, which gave a linear relation to direct determination of lecithin. For further studies of influences of cholestasis of pregnancy on the relative fatty acid composition, lecithin was chosen because differences between lecithin (PC) and phosphoglycerides (GPL) were found, evidently due to mutual variations among the three components in GPL (lecithin, cephalin and lyso‐lecithin).

Some aspects of the relationship between oral contraceptives, lipid abnormalities, and cardiovascular disease.

Most epidemiologic studies suggest an association between current use of combined oral contraceptives and certain manifestations of cardiovascular disease. Most of the data relate to older preparations little used today. Decreased levels of high-density lipoprotein cholesterol and increased amounts of low-density lipoprotein cholesterol were common findings with the older formulations. More recent experimental and epidemiologic data suggest that the potential risk of cardiovascular disease in oral contraceptive users is hardly predicated on an arteriosclerosis basis but related more to thromboembolic events. Because changes in the serum lipid profile are often associated with alterations in the factors of hemostasis, it seems reasonable to suggest the use of preparations void of profound changes in lipid metabolism, especially when other means of efficacy are available inclusive of the newer low-dose oral contraceptives. When risk factors for cardiovascular disease are present, determination of total cholesterol is desirable. In subjects with elevated serum cholesterol, a serum lipid profile should be determined. A woman at risk of cardiovascular disease should be carefully monitored, and repeated lipid determinations are recommended.