RESUMO
The influence of menstrual cycle phases and hormonal contraception on serum lipid and apolipoprotein (apo) levels was investigated in a group of normally menstruating young women. The study period covered a normal menstrual cycle (pretherapy), the fourth cycle of treatment with a triphasic oral contraceptive (OC) preparation, and the cycle immediately following interruption of therapy (cycle 5, posttherapy). Cycle phases were defined on the basis of serum hormone levels and basal body temperature determinations. Significant differences in cholesterol (free and esterified) levels were observed during the menstrual phase of both the normal menstrual cycle (lower) and the OC cycle (higher), when compared with the other phases. Triglycerides, which were higher under OCs, fluctuated similarly throughout the two cycles, but phase differences did not reach statistical significance. Apo AI and apo B were both higher under OCs, and apo B followed a trend similar to cholesterol during the two cycles. During the first month after discontinuation of OCs, cholesterol levels returned progressively to baseline values, while triglycerides were only partially decreased. We conclude that cyclic fluctuations in lipid levels do occur under the influence of both endogenous and exogenous sex hormones.
PIP: Total and free cholesterol, triglycerides, and apolipoproteins apo-A1 and B were determined at precise phases of a pre-therapy menstrual cycle, the 4th cycle on a triphasic oral contraceptive, and in the 1st post-therapy menstrual cycle in 18 women. The triphasic pill contained 5 mcg ethinyl estradiol and 180, 215 and 250 mcg norgestimate for 7 days each (ORF 10131 Triphasic, Ortho Pharmaceuticals, Raritan, NJ). Total cholesterol and triglycerides were measured enzymatically by autoanalyzer (Abbott Bichromatic Analyzer 100), free cholesterol by commercial kit (Boehringer-Mannheim, Mannhein, Germany), and apolipoproteins by electroimmunoassay (Hydragel Apo A1/B, Sebia, Issy- les-Moulineaux, France), with strict quality control using commercial standards. Sera were sampled in 4 phases: Days 3, 4 or 5 of menses, in the follicular phase during rising or peak estradiol levels, at ovulation at peak or highest LH level, and in luteal phase at peak progesterone level. In pill cycles, sera were sampled during each week. Total cholesterol was significantly lower in the menstrual phase, rose on average 9.2% in follicular phase (range -6.8% to +34.4%, in 13 of 18 women), and declined only slightly in luteal phase. Free and esterified cholesterol showed a similar pattern. Triglycerides similarly were lowest in menstrual phase, but were not significantly higher during menstrual cycles. In oral contraceptive cycles, total cholesterol fell an average of 10.7% in the 1st week, and remained at that level until the next pill-free interval or upon discontinuation, when cholesterol rose 11.2%. After discontinuation of the pill, all women resumed normal ovulatory cycles and showed stepwise normalization of cholesterol. Apo-A1 was significantly higher in pill cycles and pill-free intervals than in normal menstrual cycles (p0.001 at all 4 sample points); apo-B was also significantly higher in all samples form pill cycles (p0.05-0.001). There was no correlation between cholesterol levels and any of the hormone levels measured, estradiol, progesterone, LH or FSH.
Assuntos
Apolipoproteínas/sangue , Anticoncepcionais Orais/farmacologia , Lipídeos/sangue , Ciclo Menstrual/sangue , Adulto , Apolipoproteína A-I , Apolipoproteínas A/sangue , Apolipoproteínas B/sangue , Colesterol/sangue , Feminino , Humanos , Lipoproteínas HDL/sangue , Valores de ReferênciaRESUMO
The aim for improving the progestogen component of oral contraceptives is both to increase their selectivity by obtaining a highly effective contraceptive action and to decrease the side effects related to the existing progestogens. The androgenic activity of the existing progestogens modifies the lipid metabolism, particularly a decrease in the high density lipoprotein (HDL) level, which increases the risks of cardiovascular diseases. Thus, the discovery of a progestogen with good anti-ovulatory and minimal androgenic properties would constitute an important progress in the field of oral contraception. Norgestimate (NGM) is a new progestogen presenting an exceptional profile of biological activity, and has proved to be extremely selective, as observed during the clinical trials. The studies described below have been carried out in order to confirm clinically the low androgenic activity of NGM. In two clinical trials, Norgestimate (0.25 mg) associated with 0.035 mg of ethinyloestradiol (NGM 0.25/35) was compared to norgestrel (0.30 mg) associated with 0.030 mg of ethinyloestradiol (Lo/Ovral). In the first trial (1,261 women), the following observations were made: an important increase in the HDL level compared to the base levels in the subjects taking NGM 0.25/35, and an important decrease in the HDL level in those taking Lo/Ovral. The low density lipoprotein (LDL) level increased slightly in the NGM 0.25/35 group, while a higher increase was observed in the Lo/Ovral group. Moreover, the LDL/HDL ratio translates a more favourable lipid profile in the NGM 0.25/35 group, since the values are lower than those observed for the Lo/Ovral group.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Androgênios , Norgestrel/análogos & derivados , Acne Vulgar/induzido quimicamente , Adulto , Ensaios Clínicos como Assunto , Etinilestradiol/farmacologia , Feminino , Humanos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Estudos Multicêntricos como Assunto , Norgestrel/farmacologia , Globulina de Ligação a Hormônio Sexual/análise , Aumento de PesoRESUMO
The goal in improving the progestational component of oral contraceptives (OCs) is to enhance the selectivity of the progestin by achieving a high degree of contraceptive efficacy while decreasing undesirable side effects associated with existing progestational agents. The androgenic activity of current progestins results in changes in lipid metabolism, particularly decreased levels of high-density lipoprotein cholesterol (HDL), which have been associated with an increased risk of coronary heart disease (CHD). A progestin with high antiovulatory activity and minimal androgenicity would offer a clear therapeutic advantage in oral contraception. Norgestimate (NGM) is a new progestin with a unique profile of biological activity that has demonstrated a high level of selectivity in preclinical assays. The present studies were conducted to confirm clinically the low androgenic activity of NGM. Norgestimate (0.25 mg) in combination with 0.035 mg ethinyl estradiol (NGM 0.25/35) was compared with 0.30 mg norgestrel combined with 0.030 mg ethinyl estradiol (Lo/Ovral) in two multicenter clinical studies. In the first study (1,261 women), HDL levels were significantly increased from baseline levels in NGM 0.25/35 subjects but were significantly decreased in Lo/Ovral subjects. Increases in low-density lipoprotein cholesterol (LDL) levels were moderate in the NGM 0.25/35 group and pronounced in the Lo/Ovral group. A favorable lipid profile in NGM 0.25/35 subjects was also reflected in the LDL/HDL ratios, which were significantly lower in the NGM 0.25/35 subjects than in the Lo/Ovral subjects. Sex hormone binding globulin (SHBG) binds androgens, preventing clinical expression of androgenic activity. As a result, elevations in SHBG levels reduce bioactive (unbound) androgen levels and decrease the potential for androgenic side effects.(ABSTRACT TRUNCATED AT 250 WORDS)