Lipid Metabolism Androgens and estrogens have competing effects on hepatic lipase, a liver enzyme critical to lipid metabolism. Estrogens depress low-density lipoproteins (LDL) and elevate high-density lipoproteins (HDL), changes that can be expected to reduce the risk of atherosclerosis (155). Androgens and androgenic progestins can antagonize these beneficial changes, reducing HDL and elevating LDL levels. Estrogens elevate triglyceride levels. Low-dose formulations have minimal adverse effect on lipids, and the newer formulations (with desogestrel and norgestimate as the progestin) produce potentially beneficial changes by elevating HDL and lowering LDL (156,157). Although average values of a large group show only small lipid changes with the use of current OCs, an occasional patient may have exaggerated effects. Women whose lipid values are higher than the mean before treatment are more likely to experience abnormalities during treatment (156).
Other Metabolic Effects Oral contraceptives can produce changes in a broad variety of proteins synthesized by the liver. The estrogen in OCs increases circulating thyroid-binding globulin, thereby affecting tests of thyroid function that are based on binding, increasing total thyroxine (T4) levels, and decreasing triiodothyronine (T3) resin uptake. The results of actual thyroid function tests, as measured by free T4 and radioiodine tests, are normal (158).
Endometrial Cancer and Ovarian Cancer Combination OCs reduce the risk of subsequent endometrial cancer and ovarian cancer (159,160). Two-year use of OCs reduces the risk of endometrial cancer by 40%, and 4 or more years of use reduces the risk by 60%. The evidence for this benefit continues to accumulate (161). A 50% reduction in ovarian cancer risk for women who took OCs for 3 to 4 years and an 80% reduction with 10 or more years of use was reported (162). There was some benefit from as little as 3 to 11 months of use. A review of all available studies in the world published in English through 2008 concluded that ovarian cancer risk decreased by 20% for each 4 years of use and was seen for carriers of the BRCA1 and 2 mutations as well. The benefit persisted for at least 30 years after last use (163). A similar reduction of risk of ovarian epithelial cancer was found in a prospective study from Norway and Sweden, with borderline tumor risk equally reduced. Combination OCs with less than 50 μgof EE, or less than 100 μg of mestranol and reduced doses of progestin, provided as much protection as higher dose pills (164). Today’s lower-dose 20 μg EE pills were not separately studied. Whether or not they provide the same benefit remains unproven; however, progestinonly contraceptives are reported to provide risk reduction equivalent to that of combined OCs (165).