[Progestogens].

Progestogen is a very important steroid hormone which has roles of supporting pregnancy secreted from ovary and placenta. From 1930, a lot of progestogens are compounded for clinical use. Compounded progestogens have not only progesterone effect but also estrogen, androgen and corticosteroid effects, respectively. Progestogen is used for treatment of hormone therapy of ovulation disorders. In recent clinical application, progestogens have some important effects in contraceptives, endometriosis and hormone replacement therapy.

Effect of age on oral contraceptive-induced venous thrombosis.

This study was undertaken to investigate the effect of age on oral contraceptive-induced venous thrombosis. All women seen in the University of Padua Department of Medical and Surgical Science who had had two courses of oral contraceptive therapy at different ages were included. A total of 28 subjects met these criteria. Fifteen patients had a congenital or acquired prothrombotic condition, whereas 13 women were normal subjects. The mean age at which thrombosis occurred was 33.3 and 36.3 years for women with or without a prothrombotic condition, respectively. The ages during which the women remained asymptomatic were 23.1 and 23.3 years for women with or without a predisposing defect, respectively. Thrombosis occurred, during the second course of oral contraceptive therapy, after the mean duration of 6.5 cycles or 18.4 cycles in women with or without prothrombotic defects, respectively. During the asymptomatic course, approximately the same number of women took old progestins or third-generation compounds. On the contrary, during the second period, 21 of 28 women took progestins with third-generation compounds. Age seems to plays an important role in oral contraceptive-induced venous thrombosis. In normal women, thrombosis occurred after a greater number of oral contraceptive cycles as compared with the women with prothrombotic defects. Because the majority of women took preparations that contained third-generation progestins during the second course of therapy, concomitant contributing effects of these compounds cannot be excluded.

[New gestagens--advantages and disadvantages]. / Neue Gestagene--ihre Vor- und Nachteile.

Due to their high oral bioavailability synthetic progestagens are used for therapy, hormone replacement therapy and contraception There are different types of progestogens. There are progesterone derivatives, nortestosterone derivatives (13-methyl-gonanes and 13-ethyl-gonanes), spirolactone derivatives and norpregnance derivatives which differ in their efficacy and hormonal profile. All progestagens show antiestrogenic activities, inhibit the estrogen-induced proliferation of the endometrium and, hence, decrease the risk of endometrial hyperplasia. With the exception of Dienogest, the derivatives of 19-nortestosterone are characterized by a 17-alpha-ethynyl group and show slight androgenic properties which may antagonise some estrogen-dependent alterations of hepatic serum parameters. Tibolone which is a derivative of norethynodel also belongs to this group. Among the nortestosterone derivatives, there are the so-called "Prodrugs". Prodrugs are rapidly transformed after intake to the active progestagens. Progesterone derivatives partly exert moderate androgenic or antiandrogenic effects, while the spirolactone derivative Drospirenone shows antimineralocorticoid and antiandrogenic activities. The progesterone derivatives as well as Gestodene and Desogestrel have certain glucocorticoid activities which, at the doses used, are not clinically relevant, but possibly may influence vascular function. The effects of 19-norpregnane derivatives are comparable with those of progesterone derivatives. According to their different hormonal profiles and activities, the various available progestogens allow the choice of preparations which are best suitable for the individual woman for contraception or hormone replacement therapy.

Uniqueness of oral contraceptive progestins.

PIP: Gonane progestins are more potent and, except for levonorgestrel, less androgenic than the estrane progestins that preceded them. The current, informal method for classifying oral contraceptives (OCs) as old, first generation, or second generation on the basis of their date of introduction obscures the fact that each of the gonane progestins has unique biologic properties. Recommended, instead, is the classification of OCs according to their level of androgenicity. Under such a system, norgestimate, desogestrel, and monophasic norethindrone (0.4-0.5 mg) would fall into the low category. Triphasic levonorgestrel, norethindrone (1.0 mg), norethindrone acetate (1.0 mg), and ethynodiol diacetate (1.0 mg) would be classified as having medium androgenicity, while norgestrel (0.3 mg), norethindrone acetate (1.5-2.5 mg), and levonorgestrel (0.15 mg) would fall into the high androgenicity category.^ieng

[Action of synthetic progestin].

Chemical compound that can bind the progesterone receptor in the nucleus and cause proliferative change of the endometrium is designated as progestin (gestagen, progestogen). Progesterone (natural progestin) is secreted from corpus luteum of the ovary. Synthetic progestin can be divided into two groups: (1) progesterone derivatives, such as medroxyprogesterone acetate and (2) testosterone derivatives, such as norethisterone. The former has progestane structure and a marked progestational activities but little estrogenic and androgenic activities. While, most of the testosterone derivatives keep androgenic activities and show even estrogenic activities due to its estrane structure or production of estrogen as the metabolite. Thus, understanding the characteristics of mode of action in each synthetic progestin, we should select the appropriate one for clinical treatment.

[Chemical classification of synthetic progestogens]. / Classification chimique des progestatifs de synthèse.

The bio-clinical features of synthetic progestagens (SP) are well known: the nor-steroid compounds have a potent gonadotrophin inhibitory action, which is sometimes associated with unpleasant metabolic effects, while the compounds closely related to progesterone have a reduced anti-gonadotrophin action but excellent metabolic tolerance. However, the current classification does not satisfy the major requirement of clinicians, as it does not provide any information about the activities of the various progestagens. It is also quite arbitrary, as it uses the term "gonane" in a restrictive sense, although this is the basic component of all sex steroids and it groups the 19 nortestosterone derivatives with the "pregnene" nucleus. The authors propose a classification into 4 groups : nor-testosterone derivatives, ethyl 13 derivatives, progesterone derivatives and nor-progesterone derivatives, which immediately informs the prescriber of the principal activity of the SP molecule.

[The benefit of the classification of oral contraceptives. Studies of 525 women taking oral contraceptives (author's transl)]. / Nutzen der Klassifikation hormonaler Kontrazeptiva. Studie an 525 Frauen unter hormonaler Kontrazeption.

The multiplicity of oral contraceptives suggests a classification for clinical routine. From the dosage of estrogens and gestagens in oral contraceptives, aberration indices were calculated from consideration of proliferation and transformation aspects. According to these a classification of oral contraceptives into 3 "estrogen" groups and 4 "gestagen" groups was made. Such a classification was made in 525 women taking oral contraceptives which took into consideration the following parameters: age, length of time during which oral contraceptives had been taken, subjective side-effects, sexual medical and psychometric aspects.