Skip to Content

Estradiol / levonorgestrel Side Effects

For the Consumer

Applies to estradiol / levonorgestrel: transdermal patch extended release

In addition to its needed effects, some unwanted effects may be caused by estradiol / levonorgestrel. In the event that any of these side effects do occur, they may require medical attention.

Major Side Effects

You should check with your doctor immediately if any of these side effects occur when taking estradiol / levonorgestrel:

Incidence not known:
  • Acid or sour stomach
  • anxiety
  • backache
  • belching
  • change in vaginal discharge
  • chest pain or discomfort
  • clear or bloody discharge from the nipple
  • confusion
  • cough
  • difficulty with speaking
  • difficulty with swallowing
  • dimpling of the breast skin
  • dizziness or lightheadedness
  • double vision
  • fainting
  • fast heartbeat
  • full or bloated feeling or pressure in the stomach
  • headache
  • heartburn
  • hives, itching, or rash
  • inability to move the arms, legs, or facial muscles
  • inability to speak
  • indigestion
  • inverted nipple
  • loss of appetite
  • lump in the breast or under the arm
  • 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
  • persistent crusting or scaling of the nipple
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • redness or swelling of the breast
  • slow speech
  • sore on the skin of the breast that does not heal
  • stomach discomfort, upset, or pain
  • sudden shortness of breath or troubled breathing
  • sweating
  • swelling of the abdominal or stomach area
  • tightness in the chest
  • unusual tiredness or weakness
  • vaginal bleeding
  • vomiting

Minor Side Effects

Some of the side effects that can occur with estradiol / levonorgestrel may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common:
  • Back pain
  • body aches or pain
  • breast pain
  • burning, itching, redness, skin rash, swelling, or soreness at the application site
  • chills
  • discouragement
  • ear congestion
  • feeling sad or empty
  • fever
  • heavy nonmenstrual vaginal bleeding
  • irritability
  • loss of interest or pleasure
  • loss of voice
  • nasal congestion
  • runny nose
  • sneezing
  • sore throat
  • tiredness
  • trouble concentrating
  • trouble sleeping
Less common:
  • Bladder pain
  • bloody or cloudy urine
  • blurred vision
  • cough producing mucus
  • diarrhea
  • difficult, burning, or painful urination
  • difficulty with moving
  • dizziness
  • excess air or gas in the stomach or intestines
  • frequent urge to urinate
  • general feeling of discomfort or illness
  • itching of the vagina or genital area
  • joint pain
  • lower back or side pain
  • muscle aches and pains
  • muscle pain or stiffness
  • pain during sexual intercourse
  • pain or tenderness around the eyes and cheekbones
  • passing gas
  • pounding in the ears
  • shivering
  • slow or fast heartbeat
  • sweating
  • weight gain
Incidence not known:
  • Hair loss or thinning of the hair
  • pressure in the stomach
  • swelling of the abdominal or stomach area

For Healthcare Professionals

Applies to estradiol / levonorgestrel: transdermal film extended release


Cardiovascular side effects have included myocardial infarction and stroke as well as venous thrombosis and pulmonary embolism. Hypertension has been reported in 3.3% of patients in one study.[Ref]


Dermatologic side effects have included application site reactions (40.6%) and rash (2.4%).[Ref]


Gastrointestinal side effects have included flatulence (3.8%).[Ref]


Genitourinary side effects have included urinary tract infection (3.3%), vaginal bleeding (36.8%), breast pain (18.9%), and vaginitis (1.9%).[Ref]


Musculoskeletal side effects have included back pain (6.1%) and arthralgia (4.2%).[Ref]


Oncologic side effects have included endometrial and breast cancer.[Ref]


Psychiatric side effects have included depression (5.7%) and headache (5.2%).[Ref]


Respiratory side effects have included bronchitis (4.2%), sinusitis (3.8%), and upper respiratory infection (13.2%).[Ref]


Metabolic side effects have included edema (3.8%) and weight gain (2.8%)[Ref]


General side effects have included infection (3.3%), abdominal pain (4.2%), flu syndrome (4.7%), pain (5.2%), and accidental injury (3.3%).[Ref]


Hypersensitivity side effects have included urticaria, angioedema, and anaphylactoid/anaphylactic reactions.[Ref]


1. "Product Information. Climara Pro (estradiol-levonorgestrel)." Berlex Laboratories, Wayne, NJ.

Not all side effects for estradiol / levonorgestrel may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

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.