and increases its oral potency. These medicinal chemistry advances were crucial to the
design of oral contraceptive agents.
Oral contraception based on hormonal manipulation may be achieved in three ways,
as follows.
5.9.1.1 Ovulation Inhibitors
To achieve inhibition of ovulation, a progestogen (e.g.,levonorgestrel, norethindrone,
norgestrel, norgestimate) and an oral estrogen (e.g.,ethinyl estradiol, mestranol) are com-
bined in varying amounts and/or at varying times during the menstrual cycle. The desired
contraceptive effect is due to inhibition of ovulation through the hypothalamo-pituitary
mechanism; administration of exogenous steroids during the first half of the menstrual
cycle suppresses FSH production, thereby inhibiting maturation of ovarian follicles and
preventing ovulation. Adding a progestogen allows the secretory phase of the endometrium
to be elicited, and when the exogenous steroids are temporarily withdrawn, menstruation
occurs. These combination estrogen/progestogen agents exert a secondary contraceptive
effect via alteration of the viscosity of the cervical mucus to physically impede the sperm.
These combination oral contraceptives are formulated in different “phasic” prepara-
tions. Phasic contraceptives vary the progestin dose during the cycle, mimicking its
variation under physiological conditions. Monophasic and triphasic formulations are
among the most popular. A typical monophasic oral contraceptive contains the same
dose of estrogen and progestogen (e.g., ethinyl estradiol 30 μg and levonorgestrel 150 μg)
given on 21 days of the menstrual cycle with 7 days off. A typical triphasic combina-
tion oral contraceptive varies the doses of the steroid hormones over the course of the
cycle (e.g., ethinyl estradiol 30 μg and levonorgestrel 50 μg [days 1–6]; ethinyl estra-
diol 40 μg and levonorgestrel 75 μg [days 7–11]; and ethinyl estradiol 30 μg and
levonorgestrel 125 μg [days 12–21]; inert tablets [days 22–28]).
Of the various pharmacologic approaches to contraception, the combination pills are
by far the most convenient and the most effective. In addition, several noncontraceptive
benefits are recognized for combination oral contraceptives:
HORMONES AND THEIR RECEPTORS 327