Estradiol / norethindrone Side Effects

Some side effects of estradiol / norethindrone may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to estradiol / norethindrone: transdermal patch extended release

Along with its needed effects, estradiol / norethindrone 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 estradiol / norethindrone:

More common
  • Bloating or swelling of the face, arms, hands, lower legs, or feet
  • heavy non-menstrual vaginal bleeding
  • itching of the vagina or genital area
  • pain during sexual intercourse
  • rapid weight gain
  • thick, white vaginal discharge with no odor or with a mild odor
  • tingling of the hands or feet
  • unusual weight gain or loss
Less common
  • Cough or hoarseness
  • fever or chills
  • lower back or side pain
  • painful or difficult urination
Incidence not known
  • Abdominal or stomach bloating or fullness
  • abdominal or stomach pain
  • blurred vision
  • change in vaginal discharge
  • clay-colored stools
  • clear or bloody discharge from the nipple
  • dark urine
  • diarrhea
  • dimpling of the breast skin
  • dizziness
  • gaseous abdominal or stomach pain
  • headache, severe and throbbing
  • hives
  • hoarseness
  • inverted nipple
  • irritation
  • itching
  • joint pain, stiffness or swelling
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • loss of appetite
  • lump in the breast or under the arm
  • nausea and vomiting
  • nervousness
  • pain or feeling of pressure in the pelvis
  • persistent crusting or scaling of the nipple
  • pounding in the ears
  • rash
  • recurrent fever
  • redness of the skin
  • redness or swelling of the breast
  • severe cramping of the uterus
  • slow or fast heartbeat
  • sore on the skin of the breast that does not heal
  • swelling of the eyelids, face, lips, hands, or feet
  • tightness in the chest
  • troubled breathing or swallowing
  • unpleasant breath odor
  • unusual tiredness or weakness
  • vaginal bleeding
  • vomiting of blood
  • yellow eyes or skin

Some side effects of estradiol / norethindrone 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
  • Acid or sour stomach
  • back pain
  • belching
  • body aches or pain
  • breast pain
  • burning, itching, redness, skin rash, swelling, or soreness at the application site
  • congestion
  • cramps
  • difficulty with moving
  • discouragement
  • dryness or soreness of the throat
  • excess air or gas in the stomach or intestines
  • feeling sad or empty
  • general feeling of discomfort or illness
  • headache
  • heartburn
  • heavy bleeding
  • increased clear or white vaginal discharge
  • indigestion
  • irritability
  • lack or loss of strength
  • loss of interest or pleasure
  • muscle aches and pains
  • muscle stiffness
  • pain during sexual intercourse
  • pain or tenderness around the eyes and cheekbones
  • passing gas
  • shivering
  • sneezing
  • stomach discomfort or upset
  • stuffy or runny nose
  • sweating
  • tender, swollen glands in the neck
  • thick, white vaginal discharge with no odor or with a mild odor
  • tiredness
  • trouble concentrating
  • trouble sleeping
Less common
  • Blemishes on the skin
  • difficulty having a bowel movement (stool)
  • longer or heavier menstrual periods
  • pimples
Incidence not known
  • Burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • change in color of the treated skin
  • decreased interest in sexual intercourse
  • dizziness or lightheadedness
  • dull ache or feeling of pressure or heaviness in the legs
  • feeling of constant movement of self or surroundings
  • inability to have or keep an erection
  • increased in sexual ability, desire, drive, or performance
  • increased interest in sexual intercourse
  • itching skin near damaged veins
  • loss in sexual ability, desire, drive, or performance
  • sensation of spinning
  • weight gain

For Healthcare Professionals

Applies to estradiol / norethindrone: oral tablet, transdermal film extended release


Gastrointestinal side effects have included nausea (8% to 11%), abdominal pain (6% to 7%), diarrhea (4% to 5%), flatulence (4% to 5%), and dyspepsia (1% to 5%).


General side effects have included headache (18% to 20%), asthenia (8% to 12%), back pain (9% to 11%), flu syndrome (5% to 9%), pain (4% to 6%), and accidental injury (4% to 5%). Postmarketing side effects include increased weight.


Genitourinary side effects have included breast pain (25% to 31%), dysmenorrhea (20% to 21%), vaginitis (6% to 13%), menstrual disorder (6% to 12%), suspicious Papanicolaou smear (4% to 8%), and leukorrhea (5%). Endometrial thickening (10% to 4%) and vaginal hemorrhage (26% to 12%) have also been reported. Postmarketing side effects include endometrial hyperplasia, endocervical polyp, uterine leiomyomata, fallopian tube cyst, uterine spasms, and breast cancer.


Local side effects have included reactions at the application site (2% to 6%).


Psychiatric side effects have included nervousness (3% to 6%) and depression (3% to 6%).


Respiratory side effects have included rhinitis (7% to 13%), respiratory disorder (7% to 12%), pharyngitis (4% to 10%), and sinusitis (4% to 9%).


Cardiovascular side effects include postmarketing reports of hypertension and varicose veins.


Dermatologic side effects include postmarketing reports of skin discoloration.


Hepatic side effects include postmarketing reports of jaundice cholestatic, cholelithiasis, gall bladder disorder, and increased transaminases.


Hypersensitivity side effects include postmarketing reports of angioedema and hypersensitivity.

Nervous system

Nervous system side effects include postmarketing reports of affect lability, libido disorder, migraine, vertigo, and paraesthesia.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.

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