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

Applies to conjugated estrogens: oral tablet

Other dosage forms:

• intravenous powder for solution

Along with its needed effects, conjugated estrogens (the active ingredient contained in Premarin) 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:

More common

• Heavy non-menstrual vaginal bleeding

Less common

• Body aches or pain
• chills
• cough
• difficulty with breathing
• ear congestion
• fever
• headache
• loss of voice
• nasal congestion
• runny nose
• sneezing
• sore throat
• unusual tiredness or weakness

Incidence not known

• Abdominal or stomach pain and tenderness
• acid or sour stomach
• anxiety
• backache
• belching
• bloody stools
• blurred vision
• breast tenderness, enlargement, pain, or discharge
• change in vaginal discharge
• change in vision
• changes in skin color
• chest pain or discomfort
• clay-colored stools
• clear or bloody discharge from the nipple
• confusion
• constipation
• dark urine
• diarrhea
• difficulty with speaking
• dimpling of the breast skin
• dizziness or lightheadedness
• double vision
• fainting
• fast heartbeat
• full or bloated feeling or pressure in the stomach
• headache, severe and throbbing
• heartburn
• hives
• hoarseness
• inability to move the arms, legs, or facial muscles
• inability to speak
• indigestion
• inverted nipple
• irritation
• itching
• joint pain, stiffness, or swelling
• loss of appetite
• lump in the breast or under the arm
• migraine headache
• 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
• pain, tenderness, or swelling of the foot or leg
• painful or tender cysts in the breasts
• pains in the stomach, side, or abdomen, possibly radiating to the back
• persistent crusting or scaling of the nipple
• poor insight and judgment
• problems with memory or speech
• rash
• rectal bleeding
• redness of the skin
• redness or swelling of the breast
• shortness of breath
• slow speech
• sore on the skin of the breast that does not heal
• stomach discomfort or upset
• sudden shortness of breath or troubled breathing
• sweating
• swelling of the abdominal or stomach area
• swelling of the eyelids, face, lips, hands, or feet
• tightness in the chest
• trouble recognizing objects
• trouble thinking and planning
• trouble walking
• troubled breathing or swallowing
• unpleasant breath odor
• vaginal bleeding
• vomiting
• vomiting of blood
• wheezing
• yellow eyes or skin

Some side effects of conjugated estrogens 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
• excess air or gas in the stomach or intestines
• itching of the vagina or genital area
• lack or loss of strength
• pain during sexual intercourse
• passing gas
• thick, white vaginal discharge with no odor or with a mild odor

Less common

• Increased clear or white vaginal discharge
• leg cramps

Incidence not known

• Blistering, peeling, or loosening of the skin
• cramps
• decreased interest in sexual intercourse
• diarrhea
• difficulty with moving
• heavy bleeding
• hives or welts
• inability to have or keep an erection
• increased hair growth, especially on the face
• increased in sexual ability, desire, drive, or performance
• increased interest in sexual intercourse
• irritability
• itching of the vagina or outside genitals
• joint or muscle pain
• loss in sexual ability, desire, drive, or performance
• loss of scalp hair
• mental depression
• mood changes
• muscle stiffness
• pain
• pain during sexual intercourse
• 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
• rash
• red, irritated eyes
• sores, ulcers, or white spots in the mouth or on the lips
• swelling of the breasts or breast soreness in both females and males
• thick, white curd-like vaginal discharge without odor or with mild odor
• unexpected or excess milk flow from the breasts
• weight changes

Applies to conjugated estrogens: injectable powder for injection, oral tablet, vaginal cream

-HRT is associated with a 1.3 to 3-fold increased relative risk of developing VTE, i.e., deep vein thrombosis or pulmonary embolism. This event is more likely to occur in the first year of using HRT.

-The use of estrogen-only and estrogen-progestin therapy is associated with an up to 1.5 fold increased relative risk of ischemic stroke.

-The risk of hemorrhagic stroke is not increased during use of HRT. This relative risk is not dependent on age or on duration of use, but as the baseline risk is strongly age-dependent, the overall risk of stroke in women who use HRT will increase with age.

Common (1% to 10%): Hypertension, palpitation, vasodilation

Rare (less than 0.1%): Stroke

Postmarketing reports: Deep and superficial venous thrombosis, pulmonary embolism, thrombophlebitis, myocardial infarction, stroke

Common (1% to 10%): Acne, alopecia, hirsutism, pruritus, rash, skin discoloration, sweating, fungal dermatitis

Postmarketing reports: Chloasma or melasma (may persist when drug is discontinued), erythema multiforme, erythema nodosum, loss of scalp hair

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

Uncommon (0.1% to 1%): Bloating, abdominal pain

Postmarketing reports: Vomiting, abdominal discomfort, abdominal distension

Common (1% to 10%): Pelvic pain, breast disorder, breast enlargement, breast neoplasm, breast pain, cervix disorder, dysmenorrhea, endometrial disorder, endometrial hyperplasia, leukorrhea, metrorrhagia, urinary tract infection, uterine fibroids enlarged, uterine spasm, abnormal uterine bleeding (breakthrough bleeding/spotting), vaginal dryness, vaginal hemorrhage, vaginal moniliasis, vaginitis

Uncommon (0.1% to 1%): Vaginal candidiasis, changes in menstrual flow, changes in cervical ectropion and secretion

Postmarketing reports: Increases in seize of uterine leiomyomata, change in cervical secretion, ovarian cancer, endometrial cancer, breast tenderness, breast discharge, galactorrhea, fibrocystic breast changes, breast cancer, gynecomastia in males

Common (1% to 10%): Hyperlipidemia, weight gain, increased appetite

Very rare (less than 0.01%): Hypocalcemia

Postmarketing reports: Increase or decrease in weight, glucose intolerance, aggravation of porphyria, increased triglycerides

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

Common (1% to 10%): Headache, dizziness, paresthesia, migraine, hypertonia, insomnia, nervousness

Very rare (less than 0.01%): Exacerbation of chorea

Postmarketing reports: Exacerbation of epilepsy, dementia

Common (1% to 10%): Accidental injury, asthenia, chills, flu syndrome, pain, edema, peripheral edema, generalized edema, moniliasis

Postmarketing reports: Irritability

Common (1% to 10%): Depression, emotional liabilities, anxiety

Uncommon (0.1% to 1%): Changes in libido, mood disturbances

Common (1% to 10%): Chest pain, bronchitis, increased cough, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection

Postmarketing reports: Exacerbation of asthma

Uncommon (0.1% to 1%): Gallbladder disease

Postmarketing reports: Cholestatic jaundice, pancreatitis, enlargement of hepatic hemangiomas, ischemic colitis

Uncommon (0.1% to 1%): Hypersensitivity

Rare (less than 0.1%): Anaphylactic/anaphylactoid reactions including urticaria and angioedema

Uncommon (0.1% to 1%): Intolerance to contact lenses, steepening of corneal curvature

Postmarketing reports: Retinal vascular thrombosis

Rare (0.01% to 0.1%): Breast cancer, ovarian cancer, fibrocystic breast changes, growth potentiation of benign meningioma.

Very rare (less than 0.01%): Endometrial cancer, enlargement of hepatic hemangiomas

Breast cancer:

-An up to 2-fold increased risk of having breast cancer diagnosed is reported in women taking combined estrogen-progestin therapy for more than 5 years.

-Any increased risk in users of estrogen-only therapy is substantially lower than that seen in users of estrogen-progestin combinations. The level of risk is dependent on the duration of use.

Endometrial Cancer:

-Endometrial cancer risk is about 5 in every 1000 women with a uterus not using HRT.

-In women with a uterus, use of estrogen-only HRT is not recommended because it increases the risk of endometrial cancer.

-Depending on the duration of estrogen-only use and estrogen dose, the increase in risk of endometrial cancer varied from between 5 and 55 extra cases diagnosed in every 1000 women between the ages of 50 and 65.

-Adding a progestin to estrogen-only therapy for at least 12 days per cycle can prevent this increased risk. In the Million Women Study the use of five years of combined HRT did not increase risk of endometrial cancer.

Ovarian cancer:

-Long-term use of estrogen-only and combined estrogen-progestin HRT has been associated with a slightly increased risk of ovarian cancer. In the Million Women Study 5 years of HRT resulted in 1 extra case per 2500 users.