Safety and efficacy of a combined oral contraceptive: gestodene 75 micrograms plus ethinyl estradiol 30 micrograms in Mexican women.

An open prospective clinical trial designed to evaluate the efficacy and safety of the combined hormonal oral contraceptive (OC) containing 75 micrograms gestodene plus 30 micrograms ethinyl estradiol was undertaken in a Mexican population. Sixty-nine healthy women of reproductive age took part in the study for a total of 627 woman-months of observation. The combination of gestodene and ethinyl estradiol proved its effectiveness in preventing pregnancy during the study. Side-effects were minimal and regular endometrial bleeding patterns were observed during one year of continuous use of this OC preparation. The discontinuation rate for medical reasons was 11.6% at one year. Among a sample of 10 women, the gestodene/ethinyl estradiol combination did not induce significant changes in the serum concentration of total cholesterol and LDL cholesterol after 12 months of continuous administration. An increase in serum triglycerides and HDL cholesterol was observed; this effect could be attributed to a lack of androgenic and/or the intrinsic estrogenic behavior of gestodene. It can be concluded that this preparation is highly effective as a combined oral contraceptive; it is well tolerated and might offer some advantages with respect to other oral contraceptive combinations in its short- and medium-term impact on lipid metabolism.

A multicentre comparative study of serum lipids and apolipoproteins in long-term users of DMPA and a control group of IUD users. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation Special Programme of Research, Development and Research Training in Human Reproduction.

A clinical trial was conducted in three centres to assess the effects of long-term use of the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) on lipid metabolism. Fifty women who had used DMPA at a dose of 150 mg every three months for 3 to 9 years were recruited in Bangkok, Christchurch and Mexico City. They were compared to a control group of 120 IUD users. Total cholesterol, LDL-cholesterol, HDL-cholesterol, total triglycerides, apolipoproteins AI, AII and B were measured throughout one injection interval. Significant findings differed between centres. Compared to their own centre controls, DMPA users in Bangkok had higher LDL-cholesterol levels; those in Christchurch had lower HDL-cholesterol, apolipoprotein (apo) AI and apo AI/B ratio and higher apo B levels; those in Mexico City had a lower apo AI/B ratio. Further changes were observed during the injection interval, some of which were correlated to changes in serum MPA levels. It is concluded that long-term use of DMPA induces moderate changes in lipid metabolism which are unfavourable in terms of risk for atherosclerosis. This should be borne in mind when weighing the overall risks and benefits of this contraceptive method for a potential user.

Comparative assessment of two low-dose oral contraceptives, Lo-Femenal and Lo-Estrin, in Mexican women.

This trial was designed to determine the differences in effectiveness, clinical acceptability, and one-year discontinuation rates of two low-dose oral contraceptives: Lo-Estrin (norethindrone acetate 1.5 mg plus ethinyl estradiol 0.030 mg) and Lo-Femenal (norgestrel 0.30 mg plus ethinyl estradiol 0.030 mg) in 148 Mexican women. In addition, the effects of both oral contraceptive preparations on blood lipids were prospectively evaluated in a subgroup of 41 women. The results indicated that there were no differences in pregnancy rates, discontinuation or clinical acceptability between the two groups. The lipid changes observed were minimal for the Lo-Femenal subgroup and somewhat greater for the Lo-Estrin group, mainly an increase in serum triglycerides. These changes were interpreted as estrogen induced effects of norethindrone-containing oral contraceptives. Overall, the data indicate that both Lo-Femenal and Lo-Estrin are effective and safe combined oral contraceptives.

Long-term effects of depot-medroxyprogesterone acetate on lipoprotein metabolism.

To assess the effects of depot-medroxyprogesterone acetate (DMPA) upon serum lipids and lipoproteins, a comparative study in chronic users and new acceptors was undertaken. Two groups of women of reproductive age were included in the study; group I (n = 8) was formed by new acceptors whereas, group II (n = 14) constituted DMPA users of more than five continuous years (7.0 + 2.1 years). Blood samples were taken on the day of injection and 15, 29, 57 and 92 days after the i.m. administration of 150 mg of DMPA for the measurement of total triglycerides (TG), cholesterol (CHOL) and phospholipids (PHL). In addition, the TG and CHOL content in the very low density (VLDL), low density (LDL) and high density (HDL) lipoprotein fractions obtained by ultracentrifugation were also determined. The results demonstrated a moderate increase in the serum total TG concentrations at the expense of the VLDL fraction in the group of chronic DMPA users. In both groups, the administration of DMPA induced a moderate, though not significant, decrease in total CHOL and HDL-chol, an effect that was noticed at the end of the treatment interval; the serum LDL-chol content remained unchanged. In addition, a decrease in the total serum phospholipids content was noticed after DMPA injection in both groups, which resembled the fluctuations observed in the luteal phase of normal ovulating women. The overall data indicate that acute and/or chronic DMPA administration at the dose currently employed for contraception does not induce major abnormalities in lipoproteins in serum.

A multicentre comparative study of serum lipids and lipoproteins in four groups of oral combined contraceptive users and a control group of IUD users. World Health Organization. Task Force on Oral Contraceptives.

A prospective clinical trial was conducted in three centres to assess the effects of the type and dose of progestogen, the dose of estrogen and the progestogen-to-estrogen ratio of oral contraceptives on lipid metabolism. The preparations selected contained levonorgestrel 250 micrograms + ethinyl estradiol 50 micrograms (Neogynon), levonorgestrel 250 micrograms + ethinyl estradiol 30 micrograms (Eugynon 30), levonorgestrel 150 micrograms + ethinyl estradiol 30 micrograms (Microgynon) or norethisterone acetate 1 mg + ethinyl estradiol 50 micrograms (Minovlar). Four-hundred-and-seven premenopausal women were randomly assigned to one of the four pill groups and compared to a control group of 119 users of a CuT220c intrauterine device. Total cholesterol, HDL-cholesterol, LDL-cholesterol and total triglycerides were monitored and the analysis includes the data of those who were followed over 48 weeks, 241 OC users and 87 IUD users. 250 micrograms of levonorgestrel were found to induce more unfavourable lipid changes in terms of atherosclerotic risk than 1mg of norethisterone acetate. Levonorgestrel was found to have a dose-effect on HDL-cholesterol and LDL-cholesterol serum levels, while ethinyl estradiol had a dose-effect on serum triglycerides. HDL-cholesterol was related to the progestogen-to-estrogen ratio. Most of these findings were consistent across centres. Finally, some comments are made on the implications of the study results on the design of future lipid studies.

Variations in serum lipids and lipoproteins throughout the menstrual cycle.

One hundred fourteen women of reproductive age were included in a cross-sectional study with the aim of establishing the variations in serum lipids and lipoproteins during the menstrual cycle. Total cholesterol, triglycerides, and phospholipids were determined in whole serum and in the following lipoprotein fractions: very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins, obtained by ultracentrifugation. A significant decrease was found in total cholesterol (P less than 0.05) and phospholipids (P less than 0.01) during the late luteal phase. The LDL cholesterol decreased during the luteal phase and VLDL cholesterol increased in the early and midluteal phases. The LDL phospholipids and VLDL triglycerides also showed a significant decrease during the luteal phase (P less than 0.01). The results of this investigation demonstrate major fluctuation in cholesterol, triglyceride, and phospholipid-lipoprotein composition during the menstrual cycle.

Regulation of production and release of lipoprotein by the perfused rat liver.

The relationship between protein and triglyceride release into d < 1.007 lipoprotein was studied in the isolated perfused rat liver. Livers were perfused with a medium either high or low in linoleate content. Perfusion with the linoleate-rich medium resulted in a marked increase in the net release of both d < 1.007 lipoprotein triglyceride and lipoprotein protein, and caused a significant increase in amino acid incorporation into the protein moiety. Amino acid incorporation into d 1.008-1.21 protein was not affected by fatty acid concentration, while incorporation into whole perfusate and tissue proteins was depressed by a perfusate high in fatty acid content. Electron microscopic studies demonstrated that the livers with the higher rate of triglyceride release also produced a greater number of lipoprotein particles. The particles they released were also somewhat larger. These studies suggest that the intracellular concentration of newly esterified triglyceride and (or) some other lipid metabolite can specifically influence the release and perhaps the synthesis of d < 1.007 lipoprotein protein. They also suggest that the liver increases its rate of triglyceride release primarily by producing more lipoprotein particles.