Dienogest

Dienogest is a progestogen derived from 19-nortestosterone. It behaves as a selective agonist of the progesterone receptor: its affinity for this receptor measured in vitro remains low, on the order of 10% of that of progesterone, yet its progestational activity in the body is strong. It does not bind to any significant degree to the receptors for estrogens, glucocorticoids or mineralocorticoids, which explains its targeted profile of action.

It also displays antiandrogenic activity: in the Hershberger assay it reaches roughly 30 to 40% of that of cyproterone acetate. It is one of the few progestogens in the 19-nortestosterone family that is devoid of androgenic properties, which matters for the skin and for hair growth. From a pharmacokinetic standpoint, its oral bioavailability is high, around 90%, its peak plasma concentration is reached in about two hours, and its half-life lies between 7.5 and 10.7 hours. It is metabolized mainly in the liver by the enzyme CYP3A4, which it neither inhibits nor induces.

The primary purpose of dienogest in a combined pill is contraceptive, and this effect rests above all on the blockade of ovulation. The minimum oral dose that inhibits ovulation is close to 1 mg per day. The effect works mainly through a direct action on the ovary rather than through a strong central suppression of gonadotropins.

At a dose of 2 mg per day in the non-menopausal woman, estradiol is brought down to early follicular phase values, on the order of 30 to 50 pg/mL. Combined with an estrogen in an oral contraceptive, dienogest thus prevents the release of the egg and makes a pregnancy unlikely as long as intake remains regular. It is this suppression of ovulation that forms the basis of contraceptive efficacy.

The contraceptive combining estradiol valerate and dienogest is taken as one tablet by mouth every day, at the same time, following the order printed on the blister pack. The regimen is quadriphasic: 26 active tablets, then 2 inert tablets, and one moves from one pack straight on to the next without interruption. Taken at a fixed time, the concentration stays stable and ovulation stays inhibited.

Taking the tablet at the same moment every day helps avoid forgetting it, for instance by pairing it with a fixed daily routine. What to do if a dose is missed is set out in the leaflet and depends on the point in the cycle. The decision to start, change or stop this contraceptive is made with the doctor or midwife who prescribed it, never alone, because stopping removes the protection against pregnancy.

In the clinical trials of the estradiol valerate and dienogest combination, conducted in 2,131 women, the most frequently reported effect is headache, migraines included, in 12.7% of participants. Next come breast pain or tenderness in 7.0%, menstrual disorders in 6.9%, and nausea or vomiting in 6.0%. These manifestations are common at the start of treatment.

The other reported effects are less common: acne affects 3.9% of women, mood changes 3.0% and weight gain 2.9%. Any unusual or persistent manifestation should be reported to the professional overseeing the contraception.

The metabolism of dienogest by CYP3A4 makes it the target of interactions to watch for. Potent inducers of this enzyme reduce exposure to dienogest and can lessen contraceptive efficacy: with rifampicin, the peak concentration drops by about 52% and total exposure by about 83%. Carbamazepine, phenytoin and St John’s wort act in the same direction. Conversely, CYP3A4 inhibitors increase exposure, with ketoconazole multiplying the area under the curve by 2.86 and erythromycin by 1.62.

Monitoring includes measurement of blood pressure, with discontinuation of treatment in the event of a significant rise. Because combined oral contraceptives can reduce glucose tolerance in a dose-dependent way, women who are prediabetic or diabetic are subject to appropriate surveillance. In the presence of uncontrolled dyslipidemia, another method of contraception is considered. This monitoring is aimed precisely at spotting these situations early.

Combined oral contraceptives can shift the status of several micronutrients. One review reports a decrease in the concentrations of folate (B9), riboflavin (B2), vitamin B6, vitamin B12 and vitamin C, as well as magnesium, zinc and selenium. The magnitude of these variations and their real significance in a well-nourished person remain debated, but they outline the nutrients not to let slip.

The best-established point concerns folate. Adequate status at the start of pregnancy reduces the risk of neural tube defects, which explains the recommendation of a folic acid intake for any woman who may become pregnant, especially when stopping a contraceptive with a view to pregnancy. Fill the plate with broccoli, spinach and kale, chickpeas, beans and lentils. Vitamin B6 is found in bananas, oats and poultry, magnesium in spinach, walnuts and almonds, zinc in meat, seafood and cheese.

Eating this way covers most of the ground. When a targeted intake makes sense, it is on top of this base, in addition to your contraception and never in its place, to support the nutrients the pill tends to lower, foremost among them folate, vitamin B6, magnesium and zinc.