Ethinylestradiol

Ethinylestradiol is a synthetic estrogen. Inside cells, it binds to the estrogen receptors ERalpha and ERbeta and activates them, with an affinity comparable to or greater than that of estradiol, the body’s natural estrogen. It therefore reproduces the estrogenic signal, but in a much more stable way, which makes it active when taken by mouth and useful in a daily pill.

In a combined pill, it acts together with a progestin on the axis that links the hypothalamus and the pituitary gland, at the top of the hormonal system. Both hormones exert negative feedback: they lower the secretion of FSH and LH, the messengers that steer the ovary. Without FSH, no follicle matures; without an LH surge, no egg is released, and ovulation does not occur. The progestin also thickens the cervical mucus, which becomes hard for sperm to cross.

The combined estrogen-progestin pill is used above all to prevent pregnancy, by blocking ovulation cycle after cycle. Doctors also prescribe it beyond contraception: against heavy or irregular periods, against endometriosis, and against acne. In these indications, the steady hormonal signal eases symptoms that the natural cycle keeps alive.

It is taken as one tablet a day, at the same time. The classic schedule runs 21 active tablets followed by 7 days of break or placebo, over a 28-day cycle; some formulations are taken continuously. Taking the tablet at the same moment every day keeps concentrations stable and preserves effectiveness; a missed dose, especially at the start of a pack, reopens a window for ovulation. You should not stop it on your own without talking to your doctor.

Once swallowed, ethinylestradiol passes through the liver, where CYP3A4 transforms it, before sulfation and glucuronidation. Part of it goes back into the intestine and then returns to the liver, a back-and-forth called enterohepatic circulation. Elimination occurs for about 62 % through the stool and 38 % through the urine. Its oral bioavailability remains 38 to 48 % because of a strong first-pass effect, its half-life ranges from 7 to 36 hours, and it circulates 97 to 98 % bound to blood proteins, mainly albumin.

This hepatic passage has consequences beyond contraception. Ethinylestradiol drives the liver to make much more SHBG, the protein that carries sex hormones, up to 5 to 10 times more at high doses. It also stimulates the production of clotting factors. This stimulation explains the main risk of the treatment, venous thrombosis, which the choice of dose and monitoring seek to keep in check.

The most frequent effect involves bleeding: spotting or breakthrough bleeding between periods, especially in the first few months, while the endometrium adapts. Next come nausea, headaches, breast tenderness, water retention, weight changes and mood changes. These effects are most often temporary and ease once the body gets used to the treatment.

The serious risk to be aware of is venous thrombosis. On a combined oral contraceptive, it stands at around 60 cases per 100,000 woman-years, compared with about 30 among women who do not take one. The risk stays low in absolute terms, but it justifies spotting the situations that raise it, such as smoking, older age or a personal and family history. Pain or swelling in a calf, or sudden shortness of breath, should lead to seeking care without delay.

Several drugs change ethinylestradiol concentrations through CYP3A4. Inducers of this enzyme, such as rifampicin and certain antiepileptics (phenytoin, carbamazepine, phenobarbital, primidone), lower it and can reduce contraceptive effectiveness. Conversely, CYP3A4 inhibitors raise its concentrations. Paracetamol slows its sulfation: a 1,000 mg dose raises its exposure by about 22 %.

The influence also works the other way. Ethinylestradiol speeds up the elimination of lamotrigine, an antiepileptic, and lowers its concentrations, which may call for adjusting the dose. These interactions explain why the doctor reviews all treatments before prescribing, and why any new medication is worth reporting. Regular medical follow-up checks blood pressure and confirms that the contraception remains suited to your situation.

Food touches the same nutrients that the pill draws on. A review published in 2013 gathered the data showing that taking oral contraceptives goes along with a drop in several vitamins and minerals in the body: folate (B9), riboflavin (B2), pyridoxine (B6), cobalamin (B12), vitamin C, vitamin E, as well as magnesium, selenium and zinc. Folate is found mainly in leafy green vegetables such as spinach and kale, and in legumes such as lentils and chickpeas. Vitamin B6 comes from bananas, chickpeas and fish.

Magnesium is concentrated in nuts, almonds, pumpkin seeds and dark chocolate; zinc in pumpkin seeds, red meat and cheeses; vitamin C in oranges and berries. Folate holds a place of its own: supplementation with folic acid is advised in the months before a pregnancy to reduce the risk of a neural tube closure defect, and some combined pills are indeed fortified with it. When the plate varies little and the need rises, a targeted intake of B6, B9, zinc and magnesium makes sense, in addition to your treatment, never in its place.