Levonorgestrel, Pharmacokinetics, Efficacy and Safety 39androgen receptor, 58% that of testosterone; for the mineralocorticoid
receptor, 17% that of aldosterone; for the glucocorticoid receptor, 7.5% that of
cortisol; for the estrogen receptor, <0.02% that of estradiol [12].
LNG has about a threefold greater affinity than progesterone for the
progesterone receptor. The effect of different progestogens in the body
depends on the absorption of the drug, the duration of the presence of the drug
in the body and the activity of the drug at the target cell. Since LNG and
norgestimate have similar absorption characteristics and half-lives, the
biological activities are proportional to their affinities for the progesterone
receptor. The doses of the two progestogens for the LH and endometrial
responses correspond to their binding affinities. However, natural progesterone
is poorly absorbed and has a much shorter half-life, approximately 20 min,
and, therefore, the dose for an equivalent effect is much higher.
Similar to synthetic steroids, the specificity of the progestogens is less
than that of the natural hormones. LNG, a derivative of testosterone, has
relatively high affinity for the androgen receptor and stimulates an increase in
the rat ventral prostate weight. LNG has a higher affinity for androgen
receptors compared to other progestogens. Relative to dihydrotestosterone, the
affinities of progesterone, norgestimate, 3-ketodesogestrel, gestodene, and
LNG for the androgen receptor are 0.003, 0.005, 0.118, 0.154, and 0.220,
respectively [13].
Since 19-nortestosterone derivatives, such as gestodene and desogestrel do
not have any affinity for the estrogen receptor, it is supposed that the estrogen
activity of norethisterone, norgestrel and LNG is at least in part a consequence
of their metabolism into the 3(α,β) 5α-reduced derivatives by 5β-reductase
activity in breast cancer cells [14].
EFFICACY OF LEVONORGESTREL
All progestins have one common effect, and that is the progestogenic
effect on the estrogen-primed endometrium of rabbits. But many other
biological effects present large differences between progestins. In practice,
clinically used synthetic progestins have been selected based on activity after
oral administration, favorable bio-availability or inhibition of ovulation, but
not on pregnancy-maintaining capacity, a very important biological role for
progesterone.
LNG is the most widely utilized contraceptive progestin, alone or in
combination with EE. Marketed for the first time in the 1960s, LNG can be