Breakthrough bleeding is the most common problem in using progestational agents alone for contraception. It occurs in as many as 25% of patients. It is more frequently encountered in patients taking low-dose preparations than in those taking combination pills with higher levels of progestin and estrogen. The biphasic and triphasic oral contraceptives (Table 40–3) decrease breakthrough bleeding without increasing the total hormone content.
2.
Weight gain is more common with the combination agents containing androgen-like progestins. It can usually be controlled by shifting to preparations with less progestin effect or by dieting.
3.
Increased skin pigmentation may occur, especially in dark-skinned women. It tends to increase with time, the incidence being about 5% at the end of the first year and about 40% after 8 years. It is thought to be exacerbated by vitamin B deficiency. It is often reversible upon discontinuance of medication but may disappear very slowly.
4.
Acne may be exacerbated by agents containing androgen-like progestins (Table 40–2), whereas agents containing large amounts of estrogen usually cause marked improvement in acne.
5.
Hirsutism may also be aggravated by the “19-nortestosterone” derivatives, and combinations containing nonandrogenic progestins are preferred in these patients.
6.
Ureteral dilation similar to that observed in pregnancy has been reported, and bacteriuria is more frequent.
7.
Vaginal infections are more common and more difficult to treat in patients who are using oral contraceptives.
8.
Amenorrhea occurs in some patients. Following cessation of administration of oral contraceptives, 95% of patients with normal menstrual histories resume normal periods and all but a few resume normal cycles during the next few months. However, some patients remain amenorrheic for several years. Many of these patients also have galactorrhea. Patients who have had menstrual irregularities before taking oral contraceptives are particularly susceptible to prolonged amenorrhea when the agents are discontinued. Prolactin levels should be measured in these patients, since many have prolactinomas.
C. Severe Adverse Effects 1. Vascular disorders—Thromboembolism was one of the earliest of the serious unanticipated effects to be reported and has been the most thoroughly studied.
a. Venous thromboembolic disease—Superficial or deep thromboembolic disease in women not taking oral contraceptives occurs in about 1 patient per 1000 woman years. The overall incidence of these disorders in patients taking low-dose oral contraceptives is about threefold higher. The risk for this disorder is increased during the first month of contraceptive use and remains constant for several years or more. The risk returns to normal within a month when use is discontinued. The risk of venous thrombosis or pulmonary embolism is increased among women with predisposing conditions such as stasis, altered clotting factors such as antithrombin III, increased levels of homocysteine, or injury. Genetic disorders, including mutations in the genes governing the production of protein C (factor V Leiden), protein S, hepatic cofactor II, and others, markedly increase the risk of venous thromboembolism. The incidence of these disorders is too low for cost-effective screening by current methods, but prior episodes or a family history may be helpful in identifying patients with increased risk.