Carbohydrate metabolism and diabetes. Combined oral contraceptives may affect carbohydrate metabolism in two ways. The estrogen component is thought to increase glucose levels and suppress the insulin response to them. The higher the dose, the more effect (153, 156, 544). The progestin component has been hypothesized to stimulate overproduction of insulin, a suspected risk factor for atherosclerosis (96, 544, 545).

In low-dose OC users with initially normal blood sugar levels, these responses seldom exceed the normal range. These women face no apparent risk of developing diabetes (143, 152, 158, 171, 185, 385).

Can women with diabetes use combined OCs? Diabetics, whose insulin response to increases in glucose is already suppressed, may still be able to use low-dose OCs, depending on the severity of their diabetes. If they are insulin-dependent, their insulin requirement may increase, although with low-dose pills this does not appear to happen often (48, 305). Diabetics with known vascular disease or women who have had diabetes for over 20 years (and therefore may have suffered vascular damage) generally should choose another family planning method (557). Women with a history of diabetes during pregnancy or a family history of diabetes can safely use combined OCs without special medical supervision (48, 177, 189, 190, 228, 280, 538).

Gallbladder disease. OCs probably do not cause gallbladder disease, but instead they may accelerate the development of gallstones in already susceptible women. Gallstones are caused by abnormally high saturation of bile with cholesterol. Cholesterol saturation is higher in OC users than nonusers, possibly due to estrogen (432, 526).

After finding a higher risk during the early years of OC use, the major cohort studies did not detect any elevated risk of gallbladder disease among long-term OC users. The lack of long-term risk suggests an acceleration effect in women with already high cholesterol saturation (318, 375, 494, 526). An analysis of the results of several studies from the 1970s and early 1980s concluded that OC use is associated with only a slight increase in the risk of gallbladder disease (458).

Population and Community Development Asociation

In Thailand a community-based distributor who travels by boat gives a client a packet of pills. Oral contraceptives are well suited to community-based distribution and social marketing because of their safety and because using them involves no medical procedure.

Because of concerns that OCs may worsen existing gallbladder disease, WHO recommends that women with current symptoms of the disease should choose another method if possible (538).

Noncancerous liver tumors. Noncancerous liver tumors (hepatocellular adenomas), which are rare, are somewhat more frequent in OC users than in nonusers. They can be fatal if untreated (483). Their incidence increases with higher estrogen dose and longer OC use. Studies in the 1970s of women using higher-dose pills estimated that three cases attributable to OCs would occur per 100,000 users per year. With today's low-dose OCs, this rate may be lower (277), but new studies have not been conducted. (See Liver Cancer for discussion of liver cancer and OCs.)