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.

Oestrogen-free oral contraception with a 4 mg drospirenone-only pill: new data and a review of the literature

“…Pharmacological properties Drospirenone is a synthetic progestin, chemically belonging to the spirolactone group. Unlike other progestins, drospirenone has antimineralocorticoid, antiestrogenic, antiandrogenic and antigonadotropic partial activities [12]. The biochemical and pharmacological profile of drospirenone therefore closely matches the profile of progesterone.…”

Multicenter, phase III trials on the contraceptive efficacy, tolerability and safety of a new drospirenone‐only pill

“…Therefore, progestogen‐only contraceptives can be used in women for whom combined hormonal contraceptives are contraindicated (World Health Organization [WHO] Medical Eligibility Criteria [MEC] for contraceptive use, Category 4) or where the use of COC is not advised (WHO MEC, Category 3) . The most frequent side effect of the continuous use of progestogens is irregular bleeding …”

“…4 The most frequent side effect of the continuous use of progestogens is irregular bleeding. 6 The progestogen-only pill (POP) containing 75 μg desogestrel daily is taken continuously without a 7-day break. Desogestrel inhibits ovulation and is as effective as combined hormonal contraceptives.…”

Bleeding profile of women using a drospirenone-only pill 4 mg over nine cycles in comparison with desogestrel 0.075 mg

“…In comparison to COCPs, POPs offer several advantages. The most relevant are: a decreased venous thromboembolism (VTE) risk [1,2] and fewer metabolic changes [3]. This makes them a suitable option for women who are intolerant to or contraindicated for estrogens (due to migraine or cardiovascular risk factors such as hypertension, hyperlipidemias, obesity, diabetes, smoking habits, etc.)…”