The clinical relevance of progestogens in hormonal contraception: Present status and future developments

Abstract

The contraceptive pill is an effective and very safe method to control pregnancies. It was developed 60 years ago, and despite, that the composition has been the same since it was first developed (estrogen and progestogen), along the years the concentration of ethinyl estradiol has been reduced to improve tolerability. Nevertheless, progestogens are the basic active agent of hormonal contraception. The mechanism of progestogens is a multimodal one and basically three modes of contraceptive action can be distinguished: (a) A strong antigonadotrophic action leading to the inhibition of ovulation. The necessary dosage of ovulation inhibition per day is a fixed dosage that is inherent to each progestogen and independent of the dosage of estrogen used or the partial activities of the progestogen or the mode of application. (b) Thickening of the cervical mucus to inhibit sperm penetration and (c) Desynchronization of the endometrial changes necessary for implantation. The on the market available progestogens used for contraception are either used in combined hormonal contraceptives (in tablets, patches, or vaginal rings) or as progestogen only contraceptives. Progestogen only contraceptives are available as daily oral preparations, monthly injections, implants (2-3 years), and Intrauterine Systems (IUS). Even the long acting progestogens are highly effective in typical use and have a very low risk profile, with few contraindications. According to their introduction into the market progestogens, in combined hormonal contraceptives, have been described as first, second, third and fourth generation progestogens. Also, progestogens can be derived from testosterone, progesterone, and spironolactone that determine pharmacodynamic and pharmacokinetic differential effects. These effects contribute to the tolerability and additional beneficial or therapeutic effects whether used in combined oral contraceptives COC or as progestogen only drugs enhancing the individual options for different patient profiles. The new development of polymers for vaginal rings allowed on one side the improvement of the estrogen/progestogen combination in these rings especially regarding the comfort of use for women (avoiding of cold chain use or packages with up to six-month rings e.g.) and on the other side the development of progestogen only formulations. Another future development will be the introduction of new progestogen only pills that will provide effective contraceptive protection with more favourable bleeding patterns and a maintenance of ovulation inhibition after scheduled 24-h delays in pill intake than the existing pop with desogestrel.

Keywords: contraception; pharmakokinetik; progestogen.