Conjugated Estrogens (Cenestin, Enjuvia, Estrace, and Others)

What are conjugated estrogens?

Conjugated estrogens are mixtures of man-made or natural estrogens used as an
external source and replacement for the natural female hormone. Estrogens have
widespread effects on many tissues in the body. Estrogens cause growth and
development of the female sexual organs and maintain female sexual
characteristics such as the growth of underarm and pubic hair, body contours,
and skeleton. Estrogens also increase secretions from the cervix and growth of
the inner lining of the uterus (endometrium).

Menopausal women produce less estrogen which leads to symptoms of hot
flashes, vaginal dryness, shrinking in vaginal tissue and painful intercourse.
Using conjugated estrogens can help treat such symptoms in menopausal women.
Conjugated estrogens can also help in prevention of bone loss in menopausal

What are examples of conjugated estrogens available in the US?

Examples of oral conjugated estrogens are:

Premarin vaginal cream is a topical form of estrogen.

Enjuvia and Cenestin are
synthetic conjugated estrogens produced from plant material.

Premarin is derived
from natural sources and blended to approximate the composition of estrogens
found in urine of pregnant horses.

What are the side effects of conjugated estrogens?

There are many side effects of conjugated estrogens. Common side effects of
conjugated estrogens are nausea, headache, pain,
swelling of breasts, weight
change, abdominal pain, anxiety, edema, vaginal bleeding, and mood disturbances.

Estrogens can cause salt (sodium) and water retention (edema). Therefore,
patients with heart failure or reduced function of their kidneys who are taking
estrogens should be carefully observed for retention of water and its

Blood clots in the legs
(deep vein
thrombosis or DVT) or lungs (pulmonary
embolism) occasionally occur in women taking
conjugated estrogens. This potentially serious complication of estrogen therapy
is dose-related, that is, it occurs more commonly with higher doses. Therefore,
the lowest effective doses that relieve symptoms should be used. Cigarette
smokers are at a higher risk for blood clots. Therefore, patients requiring
estrogen therapy should
quit smoking.

Estrogens can promote a build-up of the lining of the uterus (endometrial
hyperplasia) and increase the risk of endometrial cancer. (Women who have
undergone surgical removal of the uterus – hysterectomy – are not susceptible to
endometrial hyperplasia.) The addition of a progestin to estrogen therapy
prevents the development of
endometrial cancer.

The Women's Health Initiative found that postmenopausal women (50 to 79 years
old) taking conjugated estrogens, 0.625 mg daily, in combination with
(Provera, Depo-Provera, Depo-Sub Q Provera 104), 2.5 mg daily, for five years, had an increased risk of
heart attacks, stroke, breast cancer, and blood clots, while postmenopausal
women taking conjugated estrogens without progesterone experienced only
increased strokes but not increased blood clots, heart disease, or breast

There was an increased risk of impaired cognition and/or dementia among women
over age 65 treated with either estrogens or estrogens and medroxyprogesterone.

What drugs interact with conjugated estrogens?

Medications like St. John’s Wort, phenobarbital,
(Tegretol, Tegretol XR, Equetro, Carbatrol), and rifampin (Rifadin)
can accelerate the breakdown of conjugated estrogens, leading to low levels of
absorbed drug and reduced effectiveness. Grapefruit juice and medications like
erythromycin, clarithromycin
(Biaxin, Biaxin XL),
(Nizoral, Extina, Xolegel, Kuric), and
ritonavir can slow down the
breakdown of conjugated estrogens in the liver, leading to increased levels of
estrogens and increased estrogen side effects.

What formulations of conjugated estrogens are available?

Conjugated estrogens are available as oral tablets and topical cream.

What about taking conjugated estrogens during pregnancy or while breastfeeding?

Conjugated estrogens are not recommended during pregnancy because it may
cause birth defects in the unborn. Use of conjugated estrogens is not
recommended in nursing mothers because conjugated estrogens enter breast milk
and may have harmful effects on the newborn. Conjugated estrogens can also
affect the quality and quantity of
breast milk.

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