We prefer an oral contraceptive that contains 35 µg of ethinyl estradiol plus either
ethynodiol or desogestrel to preparations with more androgenic progestins such as
levonorgestrel or norethindrone. The effect on hair growth should be evident in several
months. Treatment should be continued for at least two years, although most women
require indefinite therapy. In women with hirsutism as a major complaint, it is also
preferable to add an antiandrogen, such as spironolactone.
This compound, known as ethinyl estradiol, is the estrogen in virtually all currently used
OCs.
Soon thereafter, ethinyl substitution of testosterone also was found to result in an orally
active compound (ethisterone). Removal of the carbon at the C-19 position of ethisterone
changed it from an androgen to a progestin. This finding resulted in the development of a
class of progestins referred to as 19-nortestosterone derivatives. Included in this class are
commonly used progestins such as norethindrone, norethindrone acetate, and
levonorgestrel. Ethynodiol diacetate, another progestin in this category, also has significant
estrogenic activity.
While OCs have several mechanisms of action, the most important for providing
contraception is estrogen-induced inhibition of the midcycle surge of gonadotropin
secretion, so that ovulation does not occur. (See "The normal menstrual cycle").
Combination OCs are potent in this regard, but progestin-only pills are not.
Another potential mechanism of contraceptive action is suppression of gonadotropin
secretion during the follicular phase of the cycle, thereby preventing follicular maturation.
However, a substantial number of women develop follicles while taking an OC that contains
30 to 35 µg of ethinyl estradiol[1]. This observation highlights the importance of preventing
the midcycle surge of gonadotropin secretion.
Combination OCs are useful for the treatment of women with hyperandrogenism (most
often due to idiopathic hirsutism and polycystic ovary syndrome). Levonorgestrel-containing
preparations may aggravate these problems, and should be avoided. These women are best
treated with an OC that contains norethindrone, ethynodiol diacetate, or a third-generation
progestin (see New progestins below).
Other "multiphasic" preparations were introduced in the late 1970s and 1980s in an attempt
to further lower the total steroid dose. An example of a biphasic pill is Ortho 10/11 which
contains a fixed dose of 35 µg of ethinyl estradiol and an increasing dose of norethindrone:
0.5 mg for 10 days and 1.0 mg for 11 days. Triphasic preparations contain varying doses of
progestin or estrogen plus progestin across the 21 days. One multiphasic preparation is an
"estrophasic" oral contraceptive (Estrostep), that contains a fixed dose of norethindrone
acetate (1 mg) and a gradually increasing dose of ethinyl estradiol (20 µg on cycle days 1 to
5, 30 µg on days 6 to 12, and 35 µg on days 13 to 21) in an effort to minimize estrogen-
related side effects [10]. Cyclessa, a triphasic preparation containing 25 ug of ethinyl
estradiol with increasing doses of desogestrel (100, 125, and 150 ug days 1 to 7, 8 to 14,
and 15 to 21, respectively) is now available. While these multiphasic regimens slightly
decrease total steroid content over the month, they have no proven clinical advantage over
monophasic preparations.
New progestins — A progestin with pure progestational activity would be ideal, because the
androgenic activity is not needed for contraception, and it increases side effects and
metabolic complications. More selective progestins have recently been developed. They
include norgestimate, desogestrel, and gestodene. These newer progestins are19-
nortestosterone derivatives, but they have some structural modifications that lower their
androgen activity. Norgestimate (eg, Ortho-Cyclen or Tri-Cyclen) and desogestrel (eg,
Desogen or Ortho-Cept) appear to be the least androgenic compounds in this class; these
Drospirenone, a new progestin, is derived from 17 alpha-spirolactone, and has both
progestogenic and antimineralocorticoid activity. An oral contraceptive (Yasmin) containing
30 µg of ethinyl estradiol and 3 mg of drospirenone has been approved by the United States
Food and Drug Administration and will be available in June 2001 [15]. In a randomized trial
in 900 women receiving Yasmin or a preparation with the same estrogen dose but with 150
µg of desogestrel for 26 months, contraceptive efficacy was similar, but mean body weight
was lower than baseline with the drospirenone pill, presumably due to its
antimineralocorticoid effect