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Generic Name: conjugated estrogens and medroxyprogesterone (KON joo GAY ted ES troe jenz and me DOX ee proe JES ter one)
Brand Names: Premphase, Prempro
Prempro (conjugated estrogens and medroxyprogesterone) is used to treat the symptoms of menopause such as hot flashes and vaginal dryness. Includes Prempro side effects, interactions and indications.
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Drug Information:
Prempro contains a combination of conjugated estrogens and medroxyprogesterone. Estrogen is a female sex hormone produced by the ovaries. Estrogen is necessary for many processes in the body. Conjugated estrogens are a mixture of estrogen hormones. Medroxyprogesterone is a form of progesterone, a female hormone important for regulating ovulation and menstruation. Prempro is used to treat menopause symptoms such as hot flashes and vaginal changes, and to prevent osteoporosis (bone loss) in menopausal women. Learn more

Prempro Side Effects

Prempro Side Effects

Note: This document contains side effect information about conjugated estrogens / medroxyprogesterone. Some of the dosage forms listed on this page may not apply to the brand name Prempro.

In Summary

Common side effects of Prempro include: depression, headache, nausea, and mastalgia. Other side effects include: dizziness, and peripheral edema. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to conjugated estrogens/medroxyprogesterone: oral tablet


Oral route (Tablet)

Estrogen with or without progestin should not be used for the prevention of cardiovascular disease or dementia. Increased risks of stroke and deep vein thrombosis in postmenopausal women (50 to 79 years) using estrogen alone have been reported. Increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and DVT in postmenopausal women (50 to 79 years) using estrogen combined with progestin have been reported. An increased risk of developing probable dementia in postmenopausal women 65 years or older has also been reported in women receiving estrogen alone or estrogen combined with progestin. Unopposed estrogens increase the risk of endometrial cancer. Adding a progestin will reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Diagnostic measures should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. Risks should be assumed to be similar for other doses, combinations, and dosage forms of estrogens and progestins. Estrogens, with or without progestins, should be prescribed at the lowest effective doses and for the shortest duration possible.

Along with its needed effects, conjugated estrogens / medroxyprogesterone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking conjugated estrogens / medroxyprogesterone:

Less common

  • Bloating or swelling of the face, arms, hands, lower legs, or feet
  • blood in the urine
  • blurred vision
  • chest pain
  • clear or bloody discharge from the nipple
  • cough or hoarseness
  • dimpling of the breast skin
  • dizziness
  • fast, irregular, pounding, or racing heartbeat or pulse
  • feeling faint, dizzy, or lightheaded
  • feeling of warmth or heat
  • fever or chills
  • flushing or redness of the skin, especially on the face and neck
  • headache
  • inverted nipple
  • lower back or side pain
  • lump in the breast or under the arm
  • nervousness
  • pain during sexual intercourse
  • painful or difficult urination
  • persistent crusting or scaling of the nipple
  • pounding in the ears
  • redness or swelling of the breast
  • severe cramping of the uterus
  • sore on the skin of the breast that does not heal
  • sweating
  • thick, white vaginal discharge with no odor or with a mild odor
  • tingling of the hands or feet
  • unusual weight gain or loss
  • vaginal bleeding that is unusual and heavy
  • vaginal or genital itching
  • vaginal yeast infection

Incidence not known

  • Absent, missed, or irregular menstrual periods
  • acid or sour stomach
  • anxiety
  • backache
  • breast pain or tenderness
  • confusion
  • constipation
  • darkened urine
  • decreased vision or other changes in vision
  • difficulty with speaking
  • double vision
  • fainting
  • heartburn
  • inability to move the arms, legs, or facial muscles
  • inability to speak
  • indigestion
  • loss of appetite
  • nausea
  • pain or discomfort in the arms, jaw, back, or neck
  • pain or feeling of pressure in the pelvis
  • pain, redness, or swelling in the arm or leg
  • painful or tender cysts in the breasts
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • slow speech
  • sudden shortness of breath or troubled breathing
  • unexpected or excess milk flow from the breasts
  • vomiting
  • yellow eyes or skin

Some side effects of conjugated estrogens / medroxyprogesterone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Back pain
  • depression
  • excess gas in the stomach or intestines
  • lack or loss of strength

Less common

  • Blemishes on the skin
  • body aches or pain
  • congestion
  • depersonalization
  • diarrhea
  • difficulty with moving
  • dry skin
  • dryness of the vagina
  • dysphoria
  • euphoria
  • excessive muscle tone
  • feeling paranoid
  • flu-like symptoms
  • fullness or swelling of the breasts
  • hair loss or thinning of the hair
  • headache, severe and throbbing
  • leg cramps
  • loss of bladder control
  • menstrual periods that are longer or heavier
  • muscle pain or stiffness
  • pain in the joints
  • pain or tenderness around the eyes and cheekbones
  • pimples or acne
  • quick to react or overreact emotionally
  • rapidly changing moods
  • rash
  • sleeplessness
  • sore mouth or tongue
  • stuffy or runny nose
  • tender, swollen glands in the neck
  • tightness of the chest or wheezing
  • trouble with sleeping
  • trouble with swallowing
  • vaginal discharge that is clear or white
  • voice changes
  • white patches in the mouth or on the tongue

Incidence not known

  • Changes in appetite
  • hives or welts
  • inability to have or keep an erection
  • increased hair growth, especially on the face
  • increased interest in sexual intercourse
  • irritability
  • loss in sexual ability, desire, drive, or performance
  • loss of scalp hair
  • pain in the ankles or knees
  • painful, red lumps under the skin, mostly on the legs
  • patchy brown or dark brown discoloration of the skin
  • redness of the skin
  • weight changes

For Healthcare Professionals

Applies to conjugated estrogens / medroxyprogesterone: oral tablet


The most commonly reported adverse events have included abdominal pain, asthenia, back pain, headache, flatulence, nausea, depression, pruritus, breast pain, dysmenorrhea, and leukorrhea.


The Women's Health Initiative (WHI) sub-study reports an increased risk of deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction in postmenopausal women 50 to 79 years old with a duration of 5.6 years of daily conjugated estrogen 0.625 mg-medroxyprogesterone 2.5 mg use compared with placebo. The WHI estrogen-alone study reported increased risks of stroke and DVT during 7.1 years of daily conjugated estrogen treatment.

-Stroke Risk (WHI substudy; conjugated estrogen 0.625 mg-medroxyprogesterone 2.5 mg daily): A statistically significant increased stroke risk: 33 versus 25 per 10,000 women-years

-Coronary Heart Disease (WHI substudy; conjugated estrogen 0.625 mg-medroxyprogesterone 2.5 mg): A statistically non-significant increased risk: 41 versus 34 per 10,000 women-years

-Venous Thromboembolism (VTE): (WHI substudy; conjugated estrogen 0.625 mg-medroxyprogesterone 2.5 mg): A statistically significant (VTE) risk: 35 versus 17 per 10,000 women-years. Specifically, DVT: 26 versus 13 per 10,000 women-years and PE:18 versus 8 per 10,000 women-years

The Heart and Estrogen/Progestin Replacement Study (HERS) demonstrated no cardiovascular benefit in postmenopausal women with established coronary heart disease (CHD) taking daily conjugated estrogen 0.625 mg-medroxyprogesterone 2.5 mg (average follow-up of 4.1 years). In the HERS II study, an open label extension of HERS, an additional 2.7 years of follow-up showed rates of CHD remained comparable to placebo.

Common (1% to 10%): Chest pain, generalized edema, hypertension, vasodilation, edema

Uncommon (0.1% to 1%): Palpitation

Postmarketing reports: Deep and superficial venous thrombosis, pulmonary embolism, superficial thrombophlebitis, myocardial infarction, stroke, increase in blood pressure


Common (1% to 10%): Breast neoplasm

Uncommon (0.1% to 1%): Endometrial hyperplasia

Postmarketing reports: Ovarian cancer, endometrial hyperplasia, endometrial cancer, breast cancer

Breast Cancer: An increased risk of breast cancer was reported in the WHI substudy of daily conjugated estrogen 0.626 mg-medroxyprogesterone 2.5 mg use. After a mean follow-up of 5.6 years, the risk was 41 versus 33 cases per 10,000 women. In the women taking conjugated estrogen-medroxyprogesterone, invasive breast cancers were larger, were more likely to be node positive, and were diagnosed at a more advanced stage. Metastatic disease was rate and not different compared to placebo.

Ovarian Cancer: A statistically non-significant risk of ovarian cancer was reported in the WHI substudy of daily conjugated estrogen 0.626 mg-medroxyprogesterone 2.5 mg use. After a mean follow-up of 5.6 years, the risk was 4 versus 3 cases per 10,000 women. A large meta-analysis showed a significant increased risk of ovarian cancer in women using both estrogen-alone and estrogen plus progestin. The duration of hormone therapy use associated with an increased risk of ovarian cancer is unknown.


Very common (10% or more): Breast pain (up to 36%)

Common (1% to 10%): Breast enlargement

Uncommon (0.1% to 1%): Breast engorgement

Postmarketing reports: Breast tenderness, breast enlargement, breast pain, nipple discharge, galactorrhea, fibrocystic breast changes, changes in libido


Very common (10% or more): Dysmenorrhea (up to 13%)

Common (1% to 10%): Pelvic pain, cervix disorder, leukorrhea, menstrual disorder, metrorrhagia, suspicious PAP smear, vaginal moniliasis, vaginitis, uterine spasm, vaginal hemorrhage

Uncommon (0.1% to 1%): Menorrhagia, urinary incontinence, hematuria, urinary tract infection, vaginal dryness

Postmarketing reports: Abnormal uterine bleeding, dysmenorrhea or pelvic pain, increase in size of uterine leiomyomata, vaginitis, vaginal candidiasis, amenorrhea, changes in cervical secretion


Postmarketing reports: Anaphylaxis, angioedema, hypersensitivity


Common (1% to 10%): Decreased glucose tolerance (hyperglycemia), weight gain

Uncommon (0.1% to 1%): Increased appetite

Postmarketing reports: Appetite changes, weight increases and decreases, glucose intolerance, increased triglycerides


Very common (10% or more): Abdominal pain (up to 17%)

Common (1% to 10%): Diarrhea, dyspepsia, eructation, flatulence, nausea

Frequency not reported: Gallbladder disease

Postmarketing reports: Nausea, vomiting, abdominal pain, bloating, increased incidence of gallbladder disease, pancreatitis ischemic colitis


Common (1% to 10%): Pruritus, Rash

Uncommon (0.1% to 1%): Acne, alopecia, dry skin, sweating, skin discoloration

Postmarketing reports: Chloasma or melasma that may persist when drug is discontinue, erythema multiforme, erythema nodosum, loss of scalp hair, hirsutism, pruritus, urticaria, rash, acne


Common (1% to 10%): Back pain, arthralgia, leg cramps

Postmarketing reports: Arthralgia

Nervous system

In the WHIMS (Women's Health Initiative Memory Study) an ancillary study of WHI, the absolute risk of probable dementia for conjugated estrogen 0.625 mg-medroxyprogesterone 2.5 mg was 45 versus 22 cases per 10,000 women-years. These studies were conducted in women 65 to 79 years old and therefore it is unknown if this risk applies to younger postmenopausal women.

Very common (10% or more): Headache (up to 19%)

Common (1% to 10%): Migraine, dizziness, hypertonia

Postmarketing reports: Headache, migraine, dizziness, exacerbation of chorea, exacerbation of epilepsy, growth potentiation of benign meningioma


Common (1% to 10%): Emotional lability, depression, Insomnia, nervousness, anxiety

Postmarketing reports: Mental depression, mood disturbances, anxiety, irritability, dementia


Postmarketing reports: Cholestatic jaundice


Common (1% to 10%): Pharyngitis, sinusitis

Postmarketing reports: Asthma exacerbation


Common (1% to 10%): Asthenia, pain


Common (1% to 10%): Flu syndrome

Uncommon (0.1% to 1%): Infection, moniliasis

Editorial References and Review

Medically reviewed by BestRx Medical Team Last updated on 1/1/2020.

Source: Drugs.com Prempro