Effects of injectable or implantable progestin-only contraceptives on insulin-glucose metabolism and diabetes risk.

Progestin-only contraceptives administered by injection (Depo-Provera) or subcutaneous implant (Norplant) have been available to U.S. women for about a decade. Two epidemiological studies found their use associated with increased incidence of type 2 diabetes. In reviewing publications relating progestin injections and implants to glucose metabolism, 25 studies of various study designs and laboratory methods were identified that reported at least one insulin value in nondiabetic women. Research subjects were usually nonobese and often from developing countries. Of eight studies that performed sequential oral glucose tolerance tests (OGTTs) after at least 6 months of Depo-Provera or Norplant use, seven found significant elevations (approximate doubling) of insulin at 2 or 3 h after glucose challenge; the effects on fasting, half-hour, or 1-h postchallenge insulin values were less consistent. The three studies that performed sequential intravenous glucose tolerance tests (IVGTTs) on injection users all found an increased early-phase insulin response. One study used sequential hyperglycemic-hyperinsulinemic clamps to demonstrate reduced total-body glucose uptake per unit of insulin after 8 weeks of Norplant use. The metabolic studies generally did not show a reduction in the glucose tolerance of their nondiabetic subjects. However, compared with the lean and low-risk women who were usually selected for metabolic research, many U.S. women receiving these injections or implants may start out with increased insulin resistance due to greater weight, sedentary lifestyle, and family or childbearing histories. Additional research could help clarify whether exposure to injectable or implantable contraceptives leads to increased risk of type 2 diabetes and gestational diabetes in women with predisposing factors.