A multicenter comparative trial of triphasic and monophasic, low-dose combined oral contraceptives.

A comparative multicenter clinical trial of two combined oral contraceptives (OCs) was conducted at clinics located in the Sudan, Sri Lanka, Chile, the Dominican Republic and Ecuador. The trial was designed to determine if there were differences in efficacy, safety and acceptability between a triphasic and a low-dose monophasic OC. This report includes analysis of 1088 women. At each center, subjects were randomly allocated to one of the two OCs. Follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. There were two accidental pregnancies attributed to user failure reported during the study period; one in the triphasic group and one in the monophasic group. Adverse experiences were mainly minor with headaches and dizziness being the most common complaints; frequency of reports was similar in both groups. Cycle control was good in both groups with women in the triphasic group reporting fewer complaints of intermenstrual bleeding. Both OCs were safe and effective.

PIP: Researchers compared the efficacy, safety, and acceptability of a triphasic oral contraceptive (OC), Triquilar, with those of a monophasic OC, Lo-Femenal, among 1088 women attending clinics in Chile, the Dominican Republic, Ecuador, Sri Lanka, and the Sudan. Both OCs contained levonorgestrel and ethinyl estradiol. 90% of women in each group exhibited good user compliance. Only 1 unplanned pregnancy occurred in each group, and both pregnancies were attributed to user failure. The gross cumulative efficacy rates at 11 months were 0.3/100 woman-years for the triphasic OC and 0.2/100 woman-years for the monophasic OC. The continuation rate at 11 months was lower for Lo-Femenal than it was for Triquilar (80.8% vs. 84.6%), but the difference was not significant. The leading side-effect-related reason for discontinuation in both groups was headache. Another key reason for OC discontinuation in both groups was personal reasons, such as planning a pregnancy. Most women in both groups did not have menstrual complaints (78.8% for the Triquilar group and 77.1% for the Lo-Femenal group). Intermenstrual bleeding rates were low (7.6% for the Triquilar group and 9% for the Lo-Femenal group). Significant intercenter differences for women reporting intermenstrual bleeding and side effects (e.g., headaches) existed (p .05). Women from both groups at the clinic in the Sudan always had lower reports of intermenstrual bleeding than those at the other clinics. In fact, no woman discontinued OC use because of intermenstrual bleeding in the Sudan. Women in Sri Lanka reported fewer side effects than those in other countries, suggesting they could better tolerate OCs than the other women. This multicenter study's findings indicates that both Triquilar and Lo-Femenal are effective and safe. In addition, they exhibit good cycle control.

[Oral contraceptives and metabolic changes]. / Anticonceptivos orales y alteraciones metabólicas.

PIP: Sufficient evidence has accumulated to relate oral contraceptives (OCs) to various cardiovascular diseases in which metabolic alterations play a role. Although epidemiological studies have shown OC users to be at greater risk of venous thrombosis than nonusers, blood coagulation studies of OC users have yielded conflicting results due to variations in the methodologies used, the factors studied, the different formulations and doses of OCs, and the duration of use. Moreover, no satisfactory method exists of measuring coagulability in its totality, which is the sum of the effects of individual variations in coagulation factors, fibrinolysis, and platelet function. Numerous studies have shown that OC users have increased levels of several coagulation factors, which are believed to indicate hypercoagulability and increased risk of thrombosis, but the pathogenesis of venous thrombosis is complex. Accompanying changes in the fibrinolytic system can be interpreted as attempts to equilibrate the hypercoagulability induced by OCs. Further, there is no proof that in vitro changes are related to thrombosis in vivo. The alterations appear to be dose-related, produced primarily by estrogens, unrelated to duration of use, and to disappear a few months after termination of OC use. OC users have been shown repeatedly to have elevated levels of glucose and insulin, which are especially pronounced in glucose tolerance tests. The changes vary in intensity according to the dose and progestational components and the existence of other risk factors for diabetes. Deterioration of glucose tolerance appears related to duration of OC use, but serum insulin levels maintain the same initial elevations. The estrogens have been shown to have few effects on carbohydrate metabolism in the lower doses currently used. Norgestrel has the most marked effects on glucose and insulin levels, ethynodiol diacetate has moderate effects, and norethindrone has the least effect. The combination of .15 mg levonorgestrel and 30 mcg ethinyl estradiol has no effect on oral glucose tolerance and little effect on insulin secretion. It is hypothesized that OCs affect carbohydrate metabolism by decreasing the number and affinity of insulin receptors in target tissues. The mechanisms by which OCs produce undesirable effects on the cardiovascular system are not completely understood, but are believed to be related to alterations in lipid metabolism. The majority of laboratory studies have shown that OC users had elevated levels of cholesterol, triglycerides, and the (LDL) fractions, and a diminution of the high density lipoprotein (HDL) fraction, which has antiatherogenic properties. The changes are atherogenic in nature and produce a lipid profile similar to that of men and postmenopausal women, who are at greater risk of thrombotic cardiovascular disease that premenopausal women who are protected by estrogens. .^ieng

[Clinico-pathological study of the effects of contraceptive treatment with mestranol-lynestrol by a sequential type method]. / Estudio clínico-patologico de los effectos de la terapia contraceptiva con mestranol-linestrol en una modalidad del tipo secuencial.

PIP: 100 healthy fertile women, with active sexual lives and of reproductive age, were treated during 10 cycles in 1 year with mestranol-lynestrenol of the sequential type, for the purpose of determining the effectiveness of the drug as a contraceptive and study its effects on endometrial morphology, endocervical mucus, cervicovaginal cytology and urinary excretion of pregnanediol. The changes in the menstrual cycle and side effects were observed. The results obtained clearly show that the combination of mestranol-lynestrenol is an effective contraceptive (no pregnancy occurred), safe and well tolerated, with minimal side effects.^ieng

Urinary pregnanediol during the use of different contraceptive methods.

PIP: The behavior or urinary pregnanediol in 5 groups of 172 healthy females using different hormnal oral contraceptives (OCs) and 1 group using IUDs is compared with 1 untreated control group having normal biph asic cycles. In all cases 24 hour urine samples were obtained in the follicular (phase 1) and luteal (phase 2) phases of the cycle using the thin-layer Sulli movici chromatographic method. In the control group the phase 1 mean was .91 mg/ 24 hours (h) and the phase 2 mean was 2.63 mg/24h. There were no variations in the values of phase 1 among all the contraceptive groups while in the IUD group the mean of phase 2 was significantly lower than in the control group. Among combination OCs there were no differences between phases 1 and 2; all cases measured below 1.5mg/24h in phase 2. However, estrogen-free progestogen drugs showed elevated pregnanediol values in phase 2. Although an incidence of low pregnanediol values was exhibited among all contraceptive groups, those low values are constant only in the combined and sequential OCs. In progestogen-only drugs high pregnanediol values compatible with ovulation occurred in the luteal phase at an inversely proportional rate to the dose of the drug. Further studies should be undertaken to establish the correlation of these data with the effects of these compounds on ovarian function.^ieng

[Changes in carbohydrate metabolism during the administration of progestational hormones]. / Modificaciones del metabolismo de los hidratos de carbono durante la administración de progestágenos.

PIP: Changes in the levels of plasma glucose and serum insulin and growth hormone after oral and iv administration of glucose and infusion of arginine in a group of 35 carefully selected normal women were studied. The tests were performed before and during the administration of progestins of the sequential and combination type (Oracon and Ovulen, respectively), during the 2nd or 3rd cycle of treatment. The results showed that both types of treatment produced a significant increase in the serum insulin and growth hormone levels, while the plasma glucose level remained unaltered in the various tests. It would appear that these drugs produce an increase in peripheral resistance to insulin, since the insulin-glucose index rose in the growth hormone level, may also be due to an antiinsulin action and/or to changes in the production of insulin directly caused by the drugs.^ieng

[Effects of different contraceptives upon the ovulation changes of the morphological study of the ovaries].

PIP: Bilateral ovarian wedges were performed on 46 patients scheduled for laparotomies for medical reasons. Prior to the operation, the patients were divided into 5 groups and treated as follows: 1 for control (5 patients); 1 that was given 1 of 3 different combined oral contraceptives, i.e., Anovlar, Gynovlar, or Engynon (22 patients); 1 that was given Sequens (3 patients); 1 that was injected with 200 mg of norethindrone enanthate (14 cases); and 1 given IUDs (2 cases). It was established that all experienced ovulatory cycles prior to therapy. The laparotomies were done between the 22nd-28th day of the menstrual cycle; hormonal therapy was begun between the 3rd-6th day. All but 1 of the group on combined preparations had anovulatory cycles. Detained follicles Grade 3 or 4 with precocious cystic atresic involution were observed. Of the 3 on the sequential preparation, 2 had involuted cystic corpora lutea and 1 had atresic follicles with thecal luteinization. The patients who received the injectable ovulated. There were no morphological or substantial changes in the corpora lutea of the control and IUD groups.^ieng