General description

Gestodene is a steroid. It has a role as an estrogen.Gestodene, one of three new gonane progestins, is the most potent on a per weight basis in regard to progestational effects and has little or no estrogenic effect. In in vivo animal studies, gestodene also has less androgenic activity compared with progestins found in older combination oral contraceptive formulations. It binds to mineralocorticoid receptors and consequently is a competitive aldosterone inhibitor, leading to speculation that it may be beneficial In hypertensive patients. Numerous large clinical trials have shown that the combination of gestodene and ethinyl estradiol is as effective in preventing pregnancies as other oral contraceptives presently on the market. Irregular bleeding and spotting rates appear to be at least as good as older formulations. In general, studies show that the incidence of side effects associated with the progestin and estrogen components tends to be low, with very little impact on lipid and carbohydrate metabolism. Gestodene-containing oral contraceptives have been associated with small increases in clotting factors, generally because of the estrogen component, with compensatory changes in the fibrinolytic system.

Application and pharmacology

Gestodene is a progestogen hormonal contraceptive. Products containing gestoden include Meliane, which contains 20 mcg of ethinylestradio and 75 mcg of gestodene; and Gynera, which contains 30 mcg of ethinylestradio and 75 mcg of gestodene.Combined progestin–estrogen pills are an established and reliable contraceptive option used by women worldwide. Combined oralcontraceptives (COCs) containing the progestins–gestodene, desogestrel or norgestimate–were developed to minimize androgenic side effects and are considered an effective, well-tolerated contraceptive option. Gestodene achieves contraceptive efficacy with the lowest dose of any progestin in a COC, and has an established and favorable short- and long-term tolerability profile.

Unlike desogestrel and norgestimate, which are prodrugs and therefore require conversion to active metabolites for biologic action, gestodene is not a prodrug. Following oral administration, gestodene is converted to reduced (dihydro and tetrahydro) and hydroxylated metabolites; however, a substantial number of metabolites have not been identified. Gestodene is not converted to levonorgestrel, nor is it excreted in the urine in an unchanged form to any significant extent.^[1]

The efficacy of monophasic and triphasic gestodene containing COCs in preventing pregnancy appears to be similar to that of other COC combinations containing desogestrel and norgestimate[25]. The findings of noncomparative trials support an excellent contraceptive efficacy for gestodene. Monophasic gestodene, administered over six cycles, had method and user failure rates of 0.03 and 0.11%, respectively, and the corresponding Pearl Index values were 0.062 and 0.22, with more than 90% of women finding the treatment acceptable.

Synthesis

The technical route of total synthesis of 18-methylnorethyne or d-18-methylnorethyne used in industrial production is carried out according to the synthesis strategy of provincial total synthesis ABCD sequence.•D-18-Norone can also be synthesized according to the synthesis strategy of ring D-CD --ACD-ABCD sequence. The construction of chiral CD ring is optimized by chiral reagent proline. 1. 4-addition reaction is realized. It is characterized by no need for low-temperature Birch reduction reaction

Figure the systhesis route of common Gestodene and derivatives

History

Combined progestin–estrogen contraceptive pills are used by women throughout the world and provide a reliable, reversible method of contraception. Orally active, synthetic progestogens (progestins) that provide suppression of ovulation have been developed, beginning in the 1950s; they included norethynodrel and norethindrone (norethisterone). These progestins were initially used with mestranol, a synthetic estrogen, to produce the first combined oral contraceptives (COCs). Since mestranol is rapidly converted to ethinyl estradiol after its ingestion, the latter estrogen eventually replaced mestranol in COCs. Subsequently, the pharmaceutical industry began investigating the use of progestins with high progestational activity, which led to the development of COCs containing the progestin levonorgestrel. Following this, gestodene, desogestrel and norgestimate were developed and used in COCs to minimize the androgenic side effects seen with progestins such as levonorgestrel. After that, COCs containing dienogest or drospirenone as the progestational component achieved regulatory approval and were marketed.

Toxicity

The gestodene-containing monophasic and triphasic OCs have high efficacy with a low incidence of side effects. The dose of estrogen appears to be the most important parameter in determining if side effects will occur. The incidence of androgenic side effects and metabolic changes is minimal. Given the low incidence of side effects with OCs with older progestins, demonstrating even greater safety with this new OC is very difficult. However, as more women use OCs for longer periods, especially as women become older, these beneficial metabolic effects growincreasingly attractive. Optimally, new generation OCs will be demonstrated to have long-term protective benefits for cardiovascular disease. ^[2]

Reference