Пероральні контрацептиви

Although oral contraceptives may have some adverse effects, the overall risk of these effects is small. Bloating, breast tenderness, nausea, and headache are the most common adverse effects.

Patients on combined OCs may develop amenorrhea or breakthrough bleeding (bleeding while taking the active pills) with prolonged duration of use. Either of these effects may be managed by changing to a pill with a higher estrogen dose. Progestin-only pills often cause irregular vaginal bleeding.

In some women, ovulation remains inhibited for a few months after they stop taking OCs, but there is no long-term effect on fertility. OCs do not adversely affect the outcome of pregnancy when conception occurs during or after their use.

Estrogens increase aldosterone production and cause sodium retention, which can cause dose-related, reversible increases in blood pressure (BP) and in weight (up to about 2 kg). Weight gain may be accompanied by bloating and edema.

Most progestins used in OCs are related to 19-nortestosterone and are androgenic. Norgestimate, etonogestrel, and desogestrel are less androgenic than levonorgestrel, norethindrone, norethindrone acetate, and ethynodiol diacetate. Androgenic effects may include acne, nervousness, and an anabolic effect resulting in weight gain. If a woman gains > 4.5 kg/year, a less androgenic OC should be used. Newer 4th-generation antiandrogenic progestins include dienogest and drospirenone (related to spironolactone, a diuretic).

The incidence of deep venous thrombosis and thromboembolism (eg, pulmonary embolism) increases as the estrogen dose is increased. With OCs that contain 10 to 35 mcg of estrogen, risk is 2 to 4 times the risk at baseline. However, this increased risk is still much lower than the risk associated with pregnancy. The progestins in combination OCs may also affect this risk. OCs that contain levonorgestrel appear to have a lower risk than OCs that contain drospirenone or desogestrel. Risk is probably increased because steroid hormones increase production of clotting factors in the liver and increase platelet adhesion. If deep vein thrombosis or pulmonary embolism is suspected in a woman taking OCs, OCs should be stopped immediately until results of diagnostic tests can confirm or exclude the diagnosis. Also, OCs should be stopped at least 1 month before any major surgery that requires immobilization for a long time and should not be taken again until 1 month afterward. Women with a history of or at high risk for venous thromboembolism should not use OCs that contain estrogen.

Study results vary regarding use of OCs and risk of breast cancer (1). Some studies have found a small increased risk in current or recent users (2).

Risk of cervical cancer is slightly increased in women who have used OCs for > 5 years, but this risk decreases to baseline 10 years after stopping OCs (3). Whether this risk is related to a hormonal effect or to behaviors (ie, not using barrier contraception) is unclear.

Central nervous system effects of OCs may include nausea, vomiting, headache, depression, and sleep disturbances. Although increased stroke risk has been attributed to OCs, low-dose combination OCs do not appear to increase risk of stroke in healthy, normotensive, nonsmoking women. Nonetheless, if focal neurologic symptoms, aphasia, or other symptoms that may herald stroke develop, OCs should be stopped immediately. Smokers over 35 should not use contraceptives that contain estrogen because of the increased risk of myocardial infarction and/or stroke.

Although progestins may cause reversible, dose-related insulin resistance, use of OCs with a low progestin dose rarely results in hyperglycemia.

Serum high-density lipoprotein (HDL) cholesterol levels may decrease when OCs with a high progestin dose are used but usually increase when OCs with low progestin and estrogen doses are used. The estrogen in OCs increases triglyceride levels and can exacerbate preexisting hypertriglyceridemia. Most alterations in serum levels of other metabolites are not clinically significant. Thyroxine-binding globulin capacity may increase in OC users; however, free thyroxine levels, thyroid-stimulating hormone levels, and thyroid function are not affected.

Levels of pyridoxine, folate, B complex vitamins, ascorbic acid, calcium, manganese, and zinc decrease in OC users; vitamin A levels increase. None of these effects is clinically significant, and vitamin supplementation is not advised as an adjunct to OC use.

OCs should not be taken if cholestasis or jaundice developed with previous use. Women who have had cholestasis of pregnancy (idiopathic recurrent jaundice of pregnancy) may become jaundiced if they take OCs, and OCs should be used with caution.

Risk of developing gallstones does not appear to be increased by use of low-dose OCs.

Rarely, benign hepatic adenomas, which can spontaneously rupture, develop. Incidence increases as duration of use and OC dose increase; adenomas usually regress spontaneously after OCs are stopped.

Melasma occurs in some women; it is accentuated by sunlight and disappears slowly after OCs are stopped. Because treatment is difficult, OCs are stopped when melasma first appears. OCs do not increase risk of melanoma.

OCs have some very important health benefits. High- and low-dose combination OCs decrease the risk of (1)

• Endometrial cancer by 60% after at least 10 years of use

• Ovarian cancer by about 50% after 5 years of use and 80% after ≥ 10 years of use

They also decrease the risk of functional ovarian cysts, benign ovarian tumors, abnormal uterine bleeding due to ovulatory dysfunction, dysmenorrhea, premenstrual dysphoric disorder, iron deficiency anemia, and benign breast disorders. Salpingitis, which can impairs fertility, occur less frequently in OC users.

Although OCs can slow the metabolism of certain drugs (eg, meperidine), these effects are not clinically important.

Some drugs can induce liver enzymes (eg, cytochrome P-450 enzymes) that accelerate transformation of OCs to less biologically active metabolites. Women who take these drugs should not be given OCs concurrently unless other contraceptive methods are unavailable or unacceptable. These drugs include certain antiseizure drugs (most commonly phenytoin, carbamazepine, barbiturates, primidone, topiramate, and oxcarbazepine), ritonavir-boosted protease inhibitors, rifampin, and rifabutin. Lamotrigine should not be used with OCs because OCs can decrease lamotrigine levels and affect seizure control.

Before oral contraceptives are started, clinicians should take a thorough medical, social, and family history to check for potential contraindications to use. Blood pressure is measured, and a urine pregnancy test is done. OCs should not be prescribed unless blood pressure is normal and results of the urine pregnancy test are negative. A physical examination, although often done when OCs are started, is not required. However, a physical examination is recommended within 1 year of OC initiation. A follow-up visit in 3 months may be useful for discussing potential adverse effects and for rechecking blood pressure. OCs can be prescribed for 13 months at a time.

OCs may be started on the same day as the contraceptive visit (often called the quick-start method). The day of the week and time in the menstrual cycle are not important to when OCs are started. However, if OCs are started > 5 days after the first day of menses, women should use a backup contraceptive method (eg, condoms) for the first 7 days of OC use.

Progestin-only OCs must be taken every day, at the same time every day. If > 27 hours elapse between doses of a progestin-only OC, women should use a backup contraceptive method for 7 days in addition to taking the OC daily.

For combination OCs, timing is not as stringent. However, if combined OC users miss taking a pill one day, they are advised to take 2 pills the next day. If they forget to take a pill for 2 days, they should resume taking the OC each day and should use a backup contraceptive method for 7 days. If they forget to take a pill for 2 days and have had unprotected sex in the 5 days before forgetting to take the pill, they can consider taking emergency contraception.

The timing for starting combination OCs after pregnancy varies:

• After a 1st-trimester spontaneous or induced abortion: Started immediately

• For deliveries at 12 to 28 weeks gestation: Started within 1 week if women have no other significant risk factors for thromboembolism

• After a delivery at > 28 weeks: Not started until > 21 days postpartum because risk of thromboembolism is additionally increased during the postpartum period (however, should be delayed 42 days if women are exclusively breastfeeding [feeding on demand including night feedings and not supplementing with other foods] or if their risk of venous thromboembolism is increased [eg, because of a recent cesarean delivery]

In 98% of women who are exclusively breastfeeding and in whom menses does not resume, pregnancy does not occur for 6 months postpartum even when no contraception is used. However, these women are often advised to start using contraception within 3 months after delivery.

Progestin-only OCs may be used immediately postpartum.

If women have a history of a liver disorder, tests to confirm normal liver function should be done before OCs are prescribed. Women at risk of diabetes (eg, those who have a family history, who have had gestational diabetes, who have had high-birth-weight infants, or who have physical signs of insulin resistance such as acanthosis nigricans) require plasma glucose screening and a complete serum lipid profile annually. Use of low-dose OCs is not contraindicated by abnormal glucose or lipid test results, except for triglycerides > 250 mg/dL (2.8 mmol/L). Most women with diabetes mellitus may take combination OCs; exceptions are those who have vascular complications (eg, neuropathy, retinopathy, nephropathy) and those who have had diabetes for > 20 years.