Medicinal Chemistry

5.8.3 Therapeutic Uses of Estrogens

The most common use of estrogens is in birth control pills. Since estrogen is combined
with progestins in oral contraceptives, these agents are discussed in section 5.9.1.
Estrogens are also used therapeutically to replace or augment hormones whose natural pro-
duction is insufficient during menopause, in menstrual disorders, or as a result of insuffi-
cient development of the female reproductive tract. Estrogens are very useful in treating the
“hot flashes” of early menopause and in helping menopausal conditions such as atrophic
vaginitis. When used postmenopausally, estrogens may theoretically decrease the risk of
heart disease by lowering the incidence of atherosclerosis; however, this is an extremely
controversial area around which there is much debate. For example, in 2004 researchers
evaluating the use of estrogen replacement in postmenopausal women reported that it was
not achieving heart disease prevention, and may be increasing the risk of stroke; this
resulted in the National Institutes of Health (NIH) instructing participants in the estrogen-
alone study of the Women’s Health Initiative (WHI) to stop taking their study medication.
Estrogens taken after menopause have also been unequivocally shown to reduce the
severity of osteoporosis (“bone thinning”), especially in combination with exercise and
adequate nutrition.
Another therapeutic role for estrogens is in the treatment of cancer. In androgen-
dependent prostate carcinoma, estrogens are used therapeutically to suppress androgen
formation and thus tumor growth. Estrogens are also used to treat inoperable breast
cancer in men and postmenopausal women. However, antiestrogens, such as tamoxifen,
have fewer side effects and are usually preferred (see section 5.8.4).
Although estrogens can be used to treat cancer, the relationship between estrogens
and cancer is a complicated one. For example, estrogens can actually stimulate existing
breast cancers in certain premenopausal women. While no increased incidence of breast
cancer has been demonstrated for short-term estrogen therapy, a small increase in the
incidence of this tumor may occur with prolonged therapy. Several studies have also
shown an increased risk of endometrial carcinoma in certain patients taking estrogens
alone. However, the concomitant use of a progestin may prevent this increased risk and
may even reduce the likelihood of endometrial cancer. Other non-cancer side effects
associated with the administration of estrogens include migraine headaches, gallstone
formation, breast tenderness, and nausea.

5.8.4 Antiestrogens

Antiestrogens (estrogen receptor antagonists) are used for two purposes: fertility drugs
and antitumor agents. The first application is based on the fact that estradiol, the natural
hormone, inhibits the secretion of the gonadotrophic hormones LH and FSH by feed-
back inhibition. The result of this inhibition is the production of a single ovum in every
menstrual period, thus preventing overlapping pregnancies. Antiestrogens, such as
clomiphene (5.37), block this inhibition in women who are infertile because of anovu-
lation resulting from excessive estradiol production. Antiestrogens are therefore useful
in helping infertile women to become pregnant. As a complication of their use, multi-
ple pregnancies are rather common in women treated with antiestrogens. This incidence
of multiple births can rise up to 10% in women treated with antiestrogens for infertility,

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