Estroprogestative combinations - Contraception
The possibility of inhibiting ovulation by an oral progestin taken between the fifth and the twenty-fifth day of the menstrual cycle was shown by Pincus about 1960. The efficacy obtained by him was perhaps the consequence of the involontary presence of estrogen in the progestational preparation. Contraceptives are today among the most used drugs.
Combined contraceptives contain an estrogen and a progestin. They are usually used by oral route and are called oral contraceptives.
The estrogen is ethinylestradiol, used at the dose of 20 micrograms called low-strength or low-dose preparations, 30 or 35 micrograms in standard-strength or standard-dose preparations and 50 micrograms in high-strength or high-dose preparations also called first generation preparations.
The progestin, on the other hand, can be one of the various synthetic progestins: norethisterone, lynestrénol, norgestriénone, norgestrel, levonorgestrel, gestodene, desogestrel, norgestimate, or cyproterone.
The contraceptive effect of combined contraceptives is obtained:
- by inhibition of ovulation by reducing the secretion of FSH by the estrogen and LH by the progestin, which prevents the development of the follicle. The discontinuation of the intake of estroprogestin elicits a fall in the hormonal impregnation, partially responsible for menstruation.
- by modification of the endometrium made unsuitable for implantation
- by modification of the cervical mucus made unsuitable for the penetration of the spermatozoa.
Combined oral contraceptives have clearly demonstrated their contraceptive efficacy. However this efficacy, particularly with the low-dose pill, requires a regular intake and the absence of concomitant treatment by enzymatic inductive drugs likely to accelerate its catabolism. If a tablet is missed, the contraception can be insufficient.
According to the combination of ethinylestradiol and the progestin one can distinguish several types of contraception:
- The sequential contraception which consists of the intake of an estrogen alone during ten days, followed by the intake of an estroprogestative combination. This sequential contraception is effective but can increase the risk of endometrial cancers and is hardly used any more, except for contraception of short duration in women with atrophy of the endometrium.
- The common combined contraception which always contains the combination of an estrogen and a progestin either in constant quantities, or in different quantities during the cycle. There are thus preparations known as monophasic, biphasic or triphasic. In the triphasic preparations the quantity of ethinylestradiol is successively 30, 40 and 30 micrograms and that of gestodene of 50, 70 and 100 micrograms, for example.
Combined oral contraceptives are taken in general from the fifth to the twenty-fifth day of the cycle, one tablet daily, each box contains usually twenty one tablets and sometimes 28 tablets with 7 inert tablets of a colour different from that of the active tablets.
Several criteria are to be taken into account for the choice of a combined contraceptive:
- quantity of ethinylestradiol per tablet: low-dose, 20 micrograms, standard-dose, 35 micrograms and high-dose, 50 micrograms...
- properties of the progestin, in particular its possible androgenic effect. The three progestins having only little or not androgenic properties are desogestrel, gestodene and norgestimate.
- monophasic, biphasic or triphasic combination, this last closest to physiological variations
The tablets present in a same pharmaceutical presentation have a different color according to their composition. In certain presentations with apparent continuous intake, without discontinuation, there are inactive tablets.
Besides the combined oral contraceptives there are presentations for transdermal administration (norelgestromin+ethinylestradiol, Ortho-Evra*) or vaginal administration (etonogestrel +ethinylestradiol = Nuvaring*, vaginal ring installed for 3 weeks). The advantages of these presentations are not obvious.
- Emergency contraception by combined preparations
The combined norgestrel and ethinylestradiol preparation and the combined levonorgestrel and ethinylestradiol are used for oral postcoital contraception. The tablets must be taken according the recommended schedule in the first three days after unprotected intercourse.
This mode of contraception must be reserved for exceptional situations and does not replace the preventive contraception. Its adverse effects most frequently observed are nausea and vomiting.
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