Lipid Metabolic Studies in Oophorectomized Women. Effects of Three Different Progestogens

Abstract

Ten oophorectomized women (ranging in age from 27 to 45 years, having a mean age of 34.5 years with a standard deviation of 5.3) were given three different progestogens (norgestrel, norethisterone and medroxyprogesterone) in treatment periods of 3 weeks' duration immediately preceded by 3 weeks "wash out" periods. Venous blood samples were drawn before and after each treatment period. Free and total cholesterol, triglycerides and phospholipids were determined in the three lipoprotein fractions: Very low density lipoproteins (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). Individual phosphatides were determined after thin layer chromatography. In addition, the relative fatty acid composition of serum lecithin and cholesterol esters were assessed by gas-liquidchromatography. Both norethisterone and norgestrel caused a decrease in a-lipoprotein cholesterol. The relative fatty acid composition of serum lecithin revealed an increase of biochemical pathway I for liver lecithin synthesis on norgestrel and norethisterone but no major changes on medroxyprogesterone. With norgestrel an increase in serum-lysolecithin concomitant with a decrease in lecithin was observed, while the two other progestogens did not induce any significant changes. From thc present data it is suggested that the 19norcthisteronc derivatives, norethisterone and especially norgestrel, have androgen-likc influences on lipid metabolism. Medroxyprogesteronc, being a 17-&hydroxyprogcsterone, caused less changes and consequently less disturbance of lipid metabolism. Suppl. 88 (1 979) Acta Ohstet Gynecol Scand

Effects of low dosage progestin-only administration upon plasma triglycerides and lipoprotein metabolism in postmenopausal women.

“…However, the specific contribution of dl-norgestrel to the ob-served lowering of lipids is unknown. Although most reports find that oral contraceptives containing dl-norgestrel lower plasma triglycerides (4,5), this has not been universal (6)(7)(8). Levonorgestrel, the active isomer of dl-norgestrel, lowers plasma total and VLDL triglycerides in intact female rats when given alone (9), but not when combined with estradiol (10).…”

Tamoxifen and Natural Progesterone as Supplements to Low-Dose Postmenopausal Estrogen Therapy

“…To avoid the metabolic and androgenic sife effects associated with the use of some synthetic progestins [3,4,7,10], we studied the efficacy and safety of natural progester one as a sequential supplement to estrogen therapy. For the same reasons, and simulta- Table II.…”

“…However, this kind of treatment leads to the return of regular menstruation, which is considered to be unpleasant by most postmenopausal women. In addition, some commonly used progestins lead to de creased serum concentrations of high-density lipoprotein (HDL)-cholesterol [3,4], This effect is potentially undesirable, since a low HDL-cholestcrol concentration is known to be a risk factor for cardiovascular diseases [5,6]. Other adverse effects of progestins include acne, breast tenderness, and depression [7], We have previously shown that an antiestrogenic compound, clomiphene citrate, counteracts estrogen in the postmenopausal endometrium, a fact which is supported by the finding of decreased con centrations of cytosol estrogen and progestin receptors, and a change of estrogen-primed endometrium to an atrophic state [8].…”

LHRH agonists and the prevention of breast and ovarian cancer

“…The addition of a progestational agent to ERT will provide a benefit to the endometrium more comparable to COCs, and is likely to further improve bone metabolism (Lobo, 1987), but it is likely to have a deleterious effect on heart disease risk and may have a deleterious effect on breast cancer (Henderson et al, 1988;Key & Pike, 1988a). Small studies of different synthetic progestogens strongly suggest that they have an effect opposite to that of oestrogens on lipoprotein metabolism, and result in a substantial increase in LDLC and a substantial decline in HDLC (Silverstolpe et al, 1979). These progestogenic effects are dose-dependent and, at the commonly prescribed approximately equivalent doses (King & Whitehead, 1986), it appears that they negate, or even reverse, the beneficial effects of ERT (Henderson et al, 1988).…”