<unk>  <unk>  is a progestin and has effects similar to those of the hormone progesterone. It works primarily by preventing ovulation and closing off the cervix to prevent the passage of sperm. Pharmacodynamics<unk>  is a progestogen; that is, an agonist of the progesterone receptor (PR), the main biological target of the progestogen sex hormone progesterone. It is also a weak agonist of the androgen receptor (AR), the main biological target of the androgen sex hormone testosterone.<unk>  has no other important hormonal activity, including no estrogenic, glucocorticoid, or antimineralocorticoid activity. The lack of significant mineralocorticoid or antimineralocorticoid activity with<unk>  is in spite of a relatively high affinity for the mineralocorticoid receptor of as much as 75% of that of aldosterone. Due to its progestogenic activity,<unk>  has antigonadotropic effects, and is able to suppress fertility and gonadal sex hormone production in both women and men. Androgenic activity<unk>  is a weakly androgenic progestin and in women may cause androgenic side effects such as decreased sex hormone-binding globulin (SHBG) levels, decreased cholesterol levels, weight gain, and acne. In combination with a potent estrogen like ethinylestradiol however, all contraceptives containing androgenic progestins are negligibly androgenic in clinical practice and can in fact be used to treat androgen-dependent conditions like acne and hirsutism in women. This is because ethinylestradiol causes a marked increase in SHBG levels and thereby decreases levels of free and hence bioactive testosterone, acting as a functional antiandrogen. Nonetheless, contraceptives containing progestins that are less androgenic increase SHBG levels to a greater relative extent and may be more effective for such indications.<unk>  is currently the most androgenic progestin that remains used in contraceptives, and contraceptives containing<unk>  may be less effective for androgen-dependent conditions relative to those containing other progestins that are less androgenic. Other activity<unk>  stimulates the proliferation of MCF-7 breast cancer cells in vitro, an action that is independent of the classical PRs and is instead mediated via the progesterone receptor membrane component-1 (PGRMC1). Certain other progestins act similarly in this assay, whereas progesterone acts neutrally. It is unclear if these findings may explain the different risks of breast cancer observed with progesterone and progestins in clinical studies. Antigonadotropic effects In men,<unk>  causes marked suppression of circulating testosterone levels secondary to its antigonadotropic effects. Because of this, and due to its androgenic activity being only weak and hence insufficient for purposes of androgen replacement in males,<unk>  has potent functional antiandrogenic effects in men, and is able to produce associated adverse effects like decreased libido and erectile dysfunction among others. In relation to this,<unk>  has been combined with an androgen like testosterone or dihydrotestosterone when it has been studied as a hormonal contraceptive in men. Pharmacokinetics The bioavailability of<unk>  is approximately 95% (range 85 to 100%). The plasma protein binding of<unk>  is about 98%. It is bound 50% to albumin and 48% to SHBG.<unk>  is metabolized in the liver, via reduction, hydroxylation, and conjugation (specifically glucuronidation and sulfation). Oxidation occurs primarily at the C2α and C16β positions, while reduction occurs in the A ring. 5α-Dihydrolevonorgestrel is produced as an active metabolite of<unk>  by 5α-reductase. The elimination half-life of<unk>  is 24 to 32 hours, although values as short as 8 hours and as great as 45 hours have been reported. About 20 to 67% of a single oral dose of<unk>  is eliminated in urine and 21 to 34% in feces.
Levonorgestrel
Etonogestrel
Norgestrel
Desogestrel
Chloroethynylnorgestrel
Gestodene
5α-Dihydrolevonorgestrel
Norelgestromin