Use of progesterone and progestins
Progesterone
The therapeutic use of progesterone itself is its insufficient secretion, including during pregnancy.
In menstruating women, progesterone deficiency, real or relative to estrogen level, induces non specific clinical symptoms, uterine bleeding, dysmenorrhea, and must thus be confirmed by hormonal determinations.
In pregnant women, progesterone deficiency is seldom at the origin of spontaneous abortions which have many other causes. If, after a hormonal assessment, a substitutive treatment is decided, it is progesterone itself which has to be used.
After the menopause, progesterone itself is often used for replacement therapy.
Dydrogesterone is different chemically from progesterone by the existence of an additional double bond. Its properties are closely related to those of progesterone but it seems preferable in pregnant women to use progesterone itself, if necessary.
Synthetic progestins (progestagens)
Synthetic progestins have three principal therapeutic uses: treatment of luteal deficiency, contraception where they are prescribed alone or combined with ethinylestradiol and the treatment of certain tumors.
Luteal deficiency
Synthetic progestins are used for the treatment of luteal deficiency in non-pregnant women, particularly during perimenopause and for the treatment of endometriosis and certain functional bleedings.
Contraception
Under certain conditions, the intake of progestin alone without ethinylestradiol has a contraceptive effect. The progestins used as contraceptive are norethisterone, lynestrenol, norgestrienone, levonorgestrel, medroxyprogesterone.
According to the conditions of administration of the progestin one distinguishes:
- Oral progestin alone, taken daily at low dose but without interruption: this mode does not always suppress ovulation, but the permanent impregnation by progestin makes the cervical mucus unfavourable to spermatozoa motility and endometrium unsuitable to implantation. The daily treatment requires the intake of a tablet without interruption, even during menses. The concomitant intake of drugs with inductive enzymatic effect can make this mode of contraception ineffective by accelerating inactivation of the progestin. If a pregnancy occurs, there is an increased risk of extra-uterine pregnancies.
- Oral progestin alone taken discontinuously at high dose: in this mode the progestin alone is taken at high dose, but only from the fifth to the twenty-fifth day of the cycle. At high dose, in addition to the endometrial and cervical modifications, progestins inhibit ovulation through a pituitary negative feedbach mechanism. The products used are norethisterone, levonorgestrel, desogestrel and lynestrenol.
- Parenteral progestin-alone: in this mode the progestin is injected in the form of a slow-release preparation every three months. This method induces a permanent impregnation by the progestin. The first injection must be carried out between the first and the fifth day of the cycle. This mode of contraception is reserved to women unable to deal with an oral ontraceptive treatment. The products used are norethisterone and medroxyprogesterone (Depo-provera*).
- Subdermal implant of progestin alone: this mode gives a contraception of very long duration. The products used are levonorgestrel, 3-kétodésogestrel called also etonogestrel, active metabolite of desogestrel. Preparation of étonogestrel called Implanon * ensures a contraception during approximately three years.
- Intra-uterine progestin alone: in this mode the progestin is released from an intra-uterine device. The intra-uterine device contains barium to make it visible to radiological examination. This intra-uterine mode of contraception does not inhibit the ovulation and an extra-uterine pregnancy can be observed. The progestin used is levonorgestrel. There are in addition intra-uterine devices containing copper.
- Emergency contraception
evonorgestrel alone, at high dosage, is effective in emergency contraception also called post-coital contraception i.e. after a supposed fertilizing intercourse, when it is taken in the 24 or 48 hours following (pill of the following day), 2 intakes at an interval of 12 hours. Levonorgestrel alone and with a dosage higher than when it is combined with ethinylestradiol, induces less adverse effects (nausea, vomiting, dizziness) that in combination.
Antineoplastic treatment
Medroxyprogesterone in addition to its use in women as a contraceptive, is used at very high dose, for its antiestrogen effect, in the treatment of breast and endometrial cancers.
Megestrol, synthetic progestin whose chemical structure is closely related to that of medroxyprogesterone, is also used at high dose in the palliative treatment of breast cancer. It has also been used for the treatment of prostate cancer.,.
Particular progestins
Cyproterone occupies a special place among progestins: in addition to its progestational action, it has an anti-androgenic effect.
Drospirenone is a new synthetic progestin whose structure derives from that of spironolactone, which, in addition to its progestational effect has an antimineralocorticoid effect spironolactone-like and an anti-androgenic effect like cyproterone; it is combined with ethinylestradiol, as a contraceptive.
Tibolone is often classified among progestins. But, by itself and its metabolites, it has multiple effects: estrogenic, progestational and slightly androgenic. The fact that in long-term use it increases the risk of endometrial cancer suggests that its estrogenic effect is predominant, not compensated by its progestational effect.
Adverse effects of progestins
Synthetic progestins should not be used during pregnancy because, in addition to their luteomimetic properties, several of them have androgenic effects and some have estrogenic effects (cyproterone).
They can induce menstrual cycle irregularities, intermenstrual bleedings, and those which have androgenic properties, acne and an increase in pilosity.
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