In early reports the incidence of gallstones increased after the first 2 years of use, with a return to the level of the control group after 4 years. The latest data, however, have indicated that this apparent increase was due to an acceleration of gallbladder disease in women already susceptible. In other words, the overall risk of gallbladder disease is not increased, but in the first years of use disease is activated or accelerated in women who are vulnerable because of asymptomatic disease or a tendency toward gallbladder disease. The mechanism appears to be induced alterations in the composition of gallbladder bile, specifically a rise in cholesterol saturation that is presumably an estrogen effect. One anticipates a lesser effect in the forthcoming reports describing the impact of little dose oral contraceptives. Keep in mind that while studies have found a statistically significant modest increase in the relative risk of gallbladder disease, because the actual incidence of this problem is little, the effect is of low clinical importance.
The only absolute hepatic contraindication to oral contraceptive use is acute or chronic cholestatic liver disease. Cirrhosis and previous hepatitis are not aggravated. Once recovered from the acute phase of liver disease, a woman can use oral contraception.
Nausea, breast discomfort, and weight gain continue to be disturbing effects, but their incidence is significantly less with little dose oral contraception. Fortunately, these effects are most intense in the first several months of use and, in most cases, gradually disappear. Weight gain usually responds to dietary restriction, but for some patients, the weight gain is an anabolic response to the sex steroids, and discontinuation of oral contraception is the only way that weight loss can be achieved. This must be rare with little dose oral contraception because the data in published studies failure to indicate a difference in body weight between users and nonusers. There is no association between oral contraception and peptic ulcer disease or inflammatory bowel disease. Oral contraception is not recommended for patients with problems of gastrointestinal malabsorption because of the possibility of contraceptive failureure.
Chloasma, a patchy increase in facial pigment, was, at one time, found to occur in approximately 5% of oral contraceptive users. It is now a rare problem due to the decrease in estrogen dose. Unfortunately, once chloasma appears, it fades only gradually follittleing discontinuation of the pill and may never disappear completely. Skin blanching medications may be useful.

Hematologic effects include an increased sedimentation rate due to increased levels of fibrinogen, increased total iron binding capacity due to the increase in globulins, and a decrease in prothrombin time. The continuous use of oral contraceptives may prevent the appearance of symptoms in porphyria precipitated by menses. Changes in vitamin metabolism have been noted: a little nonharmful increase in vitamin A and decreases in blood levels of pyridoxine (B6) and the other B vitamins, folic acid, and ascorbic acid. Despite these changes, routine vitamin supplements have not been shown to be of benefit for women eating adequate, normal diets.
Mental depression is very rarely associated with oral contraceptives. In studies with higher dose oral contraceptives, the effect was due to estrogen interference with the synthesis of tryptophan that could be reversed with pyridoxine treatment. It seems wiser, however, to discontinue oral contraception if depression is encountered. Though infrequent, a reduction in libido is occasionally a problem and may be a cause for seeking an alternative method of contraception.
Because estrogen is known to stimulate prolactin secretion and to cause hypertrophy of the pituitary lactotrophs, it was appropriate to be concerned over a possible relationship between oral contraception and prolactin-secreting pituitary adenomas. Several case-control studies have uniformly concluded that no such relationship exists. Previous use of oral contraceptives is not related to the size of prolactinomas at presentation and diagnosis. Oral contraception can be prescribed to patients with pituitary microadenomas without fear of subsequent tumor growth.