No abstract

Despite the well-recognized association between oral contraceptives and deep venous thromboembolism, little is known about the risks associated with currently marketed formulations containing less than 50 micrograms of estrogen. To assess the venous thrombogenicity of low-estrogen oral contraceptives (those containing less than 50 micrograms of estrogen) relative to intermediate-dose (50 micrograms of estrogen) and high-dose (greater than 50 micrograms of estrogen) formulations, we conducted a cohort study of oral contraceptive users between the ages of 15 and 44 years in the Michigan Medicaid population. The period of the study was from 1980 through the third quarter of 1986. A total of 2,739,400 oral contraceptive prescriptions received by 234,218 women were analyzed. Using the low-estrogen cohort as the referent group, the age and calendar period adjusted relative risk of venous thromboembolism in users of intermediate-dose formulations was 1.5 (95% confidence interval (CI) 1.0-2.1, p = 0.04), and the relative risk in users of high-dose formulations was 1.7 (95% CI 0.9-3.0, p = 0.06). These data provide evidence that the dose-response relation between oral contraceptive estrogen and venous thromboembolism extends from 50 to 30 micrograms of estrogen, the dose range of currently marketed formulations.

We compared menstrual characteristics and constitutional factors in 268 white women with primary infertility due to endometriosis and in 3,794 white women admitted for delivery at seven collaborating hospitals from 1981 to 1983. Adjusting for confounding factors, including location, age, religion, and education, women with short-cycle lengths (less than or equal to 27 days) and longer flow (greater than or equal to one week) had more than double the risk for endometriosis compared with women with longer cycle lengths and shorter duration of flow. There was a trend for increasing risk for endometriosis to be associated with increasing menstrual pain. Adjusting for these menstrual characteristics, we found decreased risk for endometriosis associated with smoking or exercise that was largely confined to women who began either habit at an early age and were heavier smokers or more strenuous exercisers. We conclude that risk for endometriosis may relate to menstrual factors that predispose to greater pelvic contamination with menstrual products and to constitutional factors that influence endogenous hormonal levels.

No abstract

OBJECTIVE—Metformin was approved by the Food and Drug Administration in 1995 subject to the conduct of a randomized trial to evaluate the risk of lactic acidosis or other serious adverse events (SAEs) with this agent, under usual care conditions. RESEARCH DESIGN AND METHODS—The Comparative Outcomes Study of Metformin Intervention versus Conventional (COSMIC) Approach Study was a randomized, open-label, active-comparator, parallel-group, 1-year trial in type 2 diabetic patients suboptimally controlled on diet or sulfonylurea. Patients received metformin (n = 7,227) or other usual care treatments (n = 1,505). The primary end point was the incidence of SAEs, death, and hospitalization. RESULTS—SAEs occurred in 10.3% (95% CI 9.6–11.1%) of the metformin group and in 11.0% (9.5–12.7%) of the usual care group (P = 0.431). Lactic acidosis did not occur. All-cause mortality (1.1% [0.9–1.4%] vs. 1.3% [0.8–2.0%], P = 0.596) and hospitalization (9.4% [8.8–10.1%] vs. 10.4% [8.9–12.1%], P = 0.229) were similar between groups. CONCLUSIONS—The incidence of SAEs was similar between groups. Lactic acidosis was not observed. Metformin may be safely prescribed for type 2 diabetes if contraindications and warnings are respected. This study demonstrates the utility of large, simple trials for risk evaluation of treatments for common diseases.

No abstract

Women who use an intrauterine device (IUD) are at increased risk of acute pelvic inflammatory disease, but the relation of the IUD to subsequent infertility is not established. We interviewed 159 nulligravid women with tubal infertility to determine their prior use of an IUD. Their responses were compared with those of a matched group who conceived their first child at the time the infertile women started trying to become pregnant. The risk of primary tubal infertility in women who had ever used an IUD was 2.6 times that in women who had never used one (95 per cent confidence interval, 1.3 to 5.2). The observed difference between cases and controls was not uniform for different types of IUD. The relative risk associated with use of a Dalkon Shield was 6.8 (1.8 to 25.2), and that associated with use of either a Lippes Loop or Saf-T Coil IUD was 3.2 (0.9 to 12.0). The smallest elevation in risk was found among users of copper-containing IUDs (relative risk, 1.9 [0.9 to 4.0] for all women who had ever used a copper-containing IUD). The relative risk for women who used only a copper-containing IUD was 1.3 (0.6 to 3.0). We conclude that use of the Dalkon Shield (and possibly of plastic IUDs other than those that contain copper) can lead to infertility in nulligravid women.

We studied the importance of a history of appendectomy for appendicitis in 279 women with laparoscopically or surgically diagnosed tubal infertility and a control group of 957 fertile women. After controlling for the effects of age, use of an intrauterine device for contraception, a history of pelvic inflammatory disease, and other potential confounding variables, we found that no excess risk of tubal infertility was associated with a simple appendectomy without rupture. However, when the operation was reportedly for a ruptured appendix, the relative risk of tubal infertility was 4.8 (95 percent confidence interval, 1.5 to 14.9) for women who had never been pregnant and 3.2 (95 percent confidence interval, 1.1 to 9.6) for women with one or more previous pregnancies. We conclude that the early diagnosis and treatment of suspected appendicitis in girls and women of reproductive age may reduce the incidence of tubal infertility resulting from the sequelae of a ruptured appendix.