G. Silfverstolpe

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.

Differences in aspects of personality and sexuality between perimenopausal women making different choices regarding prophylactic oophorectomy at elective hysterectomy

Background.  Retrospective studies have indicated differences in sexuality and general psychological well‐being between women who have undergone hysterectomy only and those undergoing hysterectomy and oophorectomy. These differences may be the result of dissimilarities in the groups of women who choose the respective operation.

Progestogens and lipid metabolism

Most of the available knowledge concerning hormonal influences on lipid metabolism is based on measurements of serum concentrations of various lipid and lipoprotein fractions. The existence of a progestogenic influence is inferred from either clinical factors or measurements of this kind. However, between these two sets of endpoint data there are wide and disturbing gaps in our knowledge where we have only fragmentary information. A hormone’s net effect may consequently appear identical when assessed by reference to these endpoints, while the metabolic pathways leading to them could well be different. It is accordingly possible to devise a hormonal replacement regimen that will exert minimum effects on serum lipids and lipoproteins in plasma, but the combination used may not necessarily be the best one as far as metabolic action is concerned. It is, for instance, quite clear that while pregnancy is associated with vast changes in lipid metabolism, it appears to have little impact on the incidence of myocardial infarction. Both exogenously administered and endogenously produced hormones influence lipid metabolism in several ways. For instance, general well-being, physical and psychic activity as well as dietary habits, use of alcohol and tobacco may be influenced, and these are known in turn to affect lipid metabolism. Exogenously administered hormones could also influence the endogenous hormonal milieu, especially in women with an intact ovarian-hypothalamic axis. These effects can be summarised as indirect hormonal effects on lipid metabolism (Table I). Administration of a hormone implies administration of a .compound having certain defined physiological effects which are mediated by receptors. Since receptors occur in several target organs, including the brain and the liver, it is quite clear that the hormone will also have direct effects which are partly receptor-mediated. Moreover, when a compound is administered generally, it influences metabolism

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.

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)

Does Progestogen Reduction in Oral Contraception Parallel Reduced Lipid Metabolic Effects

Abstract. 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 μg of ethinylestradiol + levonorgestrel where the levonorgestrel dose is varied from 50 μg during the first 11 days up to 125 μg during the last 10 days of the cycle) was compared with Ova‐none (50 μg of ethinylestradiol for 22 days with the addition of 2.5 mg lynestrenol during the last 15 days of the cycle).

THE INFLUENCE OF HORMONAL REPLACEMENT THERAPY ON LIPID AND LIPOPROTEIN METABOLISM

Abstract. The widespread use of exogenous sex steroids for contraception, treatment of climacteric deficiency symptoms, etc., has led to the development of new compounds and combinations. Before new combinations of exogenous sex steroids or new steroidal compounds are introduced in clinical practice, evaluation of possible adverse metabolic effects should be mandatory.

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.

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.

Lipid metabolism in women with polycystic ovary syndrome: possible implications for an increased risk of coronary heart disease**Supported by grants from the Göteborg Medical Society, The Medical Faculty, University of Göteborg, and Organon, Oss, The Netherlands.

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.