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conjugated equine estrogens/medroxyprogesterone acetate, Prempro, Premphase: Drug Facts, Side Effects and Dosing

What is conjugated equine estrogens and medroxyprogesteron, and how does it work (mechanism of action)?

Prempro and Premphase are combinations of
conjugated estrogens (Premarin) and
medroxyprogesterone (Provera). Estrogens and
progestins are the two major classes of female hormones. Conjugated estrogens
are a mixture of several different estrogens (estrogen salts) that are derived
from natural sources and blended to approximate the composition of estrogens in
the urine of pregnant horses. The main components are sodium estrone sulphate
and sodium equilin sulfate. 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).
Medroxyprogesterone is a derivative of progesterone, a naturally occurring
female progestin. Progestins are responsible for changes in the mucus and inner
lining of the uterus (endometrium) during the second half (secretory phase) of
the menstrual cycle. Progestins prepare the endometrium for implantation of the
embryo. Once an embryo implants in the endometrium, for example, and pregnancy
occurs, progestins help maintain the pregnancy. At high doses, progestins can
prevent ovulation (release of the egg from the ovary) and thereby prevent
pregnancy. The FDA approved Prempro and Premphase in June 2003.

What brand names are available for conjugated equine estrogens and medroxyprogesteron?

Prempro, Premphase

Is conjugated equine estrogens and medroxyprogesteron available as a generic drug?


Do I need a prescription for conjugated equine estrogens and medroxyprogesteron?


What are the side effects of conjugated equine estrogens and medroxyprogesteron?

The most common side effects of Prempro and Premphase are:

Other important side effects include:

The Women's
Health Initiative found that postmenopausal women (50-79 years old) taking
conjugated estrogens, 0.625 mg daily, in combination with medroxyprogesterone,
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 cancer. 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 is the dosage for conjugated equine estrogens and medroxyprogesteron?

One tablet of Prempro should be taken daily. The lowest
effective dose should be used. For either hot flashes or osteoporosis, patients
are most often started at a dose of 0.3 mg/1.5 mg. For women with hot flashes,
the dose is adjusted depending on the response of the hot flashes.

should take one tablet of Premphase daily starting with the 0.625 mg conjugated
estrogen tablets for 14 days (days 1 to 14) followed by one tablet daily of the
0.625/5 mg conjugated estrogen/medroxyprogesterone tablets for 14 days (days 14
to 28).

Which drugs or supplements interact with conjugated equine estrogens and medroxyprogesteron?

Drugs such as St. John’s Wort (Hypericum perforatum),
phenobarbital, carbamazepine
(Tegretol, Tegretol XR, Equetro, Carbatrol), and rifampin may increase break-down of estrogens
in the liver, reducing blood levels of estrogens and possibly reducing the
effect of estrogens. Erythromycin, clarithromycin
(Biaxin, Biaxin XL), ketoconazole
(Nizoral, Extina, Xolegel, Kuric), itraconazole (sporanox),
(Norvir) and grapefruit juice may reduce break-down of estrogens in the liver,
increasing blood concentrations of estrogens and possibly increasing side
effects of estrogens.


If menopause occurs in a woman younger than ___ years, it is considered to be premature.
See Answer

Is conjugated equine estrogens and medroxyprogesteron safe to take if I’m pregnant or breastfeeding?

Prempro and Premphase should not be given to
pregnant women
due to the risk of harm to the fetus.

Estrogens are secreted in breast milk and cause
unpredictable effects in the infant. They should not be taken by women who are

What else should I know about conjugated equine estrogens and medroxyprogesteron?

What preparations of conjugated equine estrogens and medroxyprogesteron are available?

  • Prempro: Tablets 0.3/1.5, 0.45/1.5, 0.625/2.5, and 0.625/5 (mg
    conjugated estrogen/mg medroxyprogesterone).
  • Premphase: Tablets, 28 day pack containing 14 tablets of 0.625 mg
    conjugated estrogens and 14 tablets of 0.625 mg/5 mg (conjugated estrogen/medroxyprogesterone).
How should I keep conjugated equine estrogens and medroxyprogesteron stored?

Prempro and Premphase should be stored at room temperature
between 15-30 C (59-86 F).

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