Oral Contraceptives

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

Patients on estrogen-progestin 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 skin and hair changes and an anabolic effect resulting in weight gain. If a woman gains 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 skin and hair changes 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).include dienogest and drospirenone (related to spironolactone, a diuretic).

The incidence of venous thromboembolism (VTE) is increased about 3-fold in estrogen-progestin oral contraceptive users compared to never-users because estrogen increases hepatic production of clotting factors and increases platelet adhesion. Despite this increase, the absolute risk of VTE for estrogen-progestin OC users is low (3 to 15 per 10,000 women years), especially as compared to the absolute risk of VTE in postpartum patients (40 to 65 per 10,000 women years) (1). The progestins in estrogen-progestin OCs have minimal effect on this risk. OCs that contain levonorgestrel as the progestin appear to have a slightly lower risk than those that contain drospirenone or desogestrel but this is likely due to study participant selection factors and should not alter prescribing habits. If VTE is suspected in a person 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 prolonged period of time and should not be taken again until 1 month postoperatively. Patients expecting to be ambulatory postoperatively do not need to stop OC use. Women with a history of or at high risk for VTE should not use OCs that contain in estrogen-progestin OCs have minimal effect on this risk. OCs that contain levonorgestrel as the progestin appear to have a slightly lower risk than those that contain drospirenone or desogestrel but this is likely due to study participant selection factors and should not alter prescribing habits. If VTE is suspected in a person 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 prolonged period of time and should not be taken again until 1 month postoperatively. Patients expecting to be ambulatory postoperatively do not need to stop OC use. Women with a history of or at high risk for VTE should not use OCs that containestrogen. Universal screening for hypercoagulability factors, such as Factor V Leiden, is not recommended (2).

Study results vary regarding use of OCs and risk of breast cancer (3). Some studies have found a small increased risk in current or recent users (4).

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 (5). 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 estrogen-progestin 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.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.

Health benefits associated with OCs include decreased 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.

Drug interactions with hormonal contraceptives can decrease contraceptive efficacy or alter the therapeutic efficacy of the concurrent medications.

Contraceptive failure may occur if drug-drug interactions result in decreased serum levels of hormonal contraceptives. Concurrent use of medications that induce cytochrome P450 enzymes (CYP450) can accelerate metabolism of estrogens and/or progestins, resulting in decreased plasma concentrations and increased risk of contraceptive failure (1). Patients who take these medications should not use hormonal contraceptives, with the exception of a levonorgestrel IUD, unless other contraceptive methods are contraindicated or unavailable; efficacy of a levonorgestrel IUD is not impacted by this type of drug interaction because the hormone is delivered locally to the uterus. CYP450-inducers include medications in the following drug classes: antibiotics (). Patients who take these medications should not use hormonal contraceptives, with the exception of a levonorgestrel IUD, unless other contraceptive methods are contraindicated or unavailable; efficacy of a levonorgestrel IUD is not impacted by this type of drug interaction because the hormone is delivered locally to the uterus. CYP450-inducers include medications in the following drug classes: antibiotics (rifampin, rifabutin); antiretrovirals (efavirenz, ritonavir-boosted protease inhibitors); and anticonvulsants (eg, phenytoin, carbamazepine). The herbal supplement St. John's wort is also a CYP450-inducer. , rifabutin); antiretrovirals (efavirenz, ritonavir-boosted protease inhibitors); and anticonvulsants (eg, phenytoin, carbamazepine). The herbal supplement St. John's wort is also a CYP450-inducer.

Glucagon-like peptide-1Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists delay gastric emptying, which may decrease absorption of oral medications. For tirzepatide, a combined GLP-1/GIP agonist, there is evidence that during the initiation and dose escalation of the drug, plasma concentrations of oral contraceptives are significantly reduced (delay gastric emptying, which may decrease absorption of oral medications. For tirzepatide, a combined GLP-1/GIP agonist, there is evidence that during the initiation and dose escalation of the drug, plasma concentrations of oral contraceptives are significantly reduced (2, 3). The Society of Family Planning recommends that individuals who are taking oral contraceptives switch to a non-oral method of contraception or use backup methods for 4 weeks when initiating tirzepatide and after a dose increase (4). Clinically significant reductions in plasma concentrations of oral contraceptives have not been with use of GLP-1 agonists.

Oral contraceptives can increase renal clearance of lamotrigine, an anticonvulsant, and thus may decrease its therapeutic efficacy (Oral contraceptives can increase renal clearance of lamotrigine, an anticonvulsant, and thus may decrease its therapeutic efficacy (5).

Before oral contraceptives are started, clinicians should take a thorough medical, social, and family history to assess for potential contraindications to use. Blood pressure should be measured. A pregnancy test is not required and should be performed based on risk factors for pregnancy. OCs should not be prescribed unless blood pressure is normal and a urine pregnancy test (if indicated) is negative. A physical examination is not required prior to initiating OCs. Routine blood work is not required in patients without comorbidities. Routine screening for glucose, lipids, liver enzymes or thrombophilia is not necessary in a patient with no medical history (1).

OCs should be prescribed for 13 months at a time to limit barriers to continuous use and refills should be easily accessible.

OCs may be started on the same day as the contraceptive visit (often called the quick-start method), regardless of the day of the week or the time in the menstrual cycle. 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.

A follow-up visit in 3 months may be useful for discussing potential adverse effects and for rechecking blood pressure.