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Ena Side Effects

Generic Name: estradiol / norethindrone

Note: This document contains side effect information about estradiol / norethindrone. Some of the dosage forms listed on this page may not apply to the brand name Ena.

For the Consumer

Applies to estradiol / norethindrone: oral tablet

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
  • Body aches or pain
  • chills or fever
  • cold or flu-like symptoms
  • difficulty breathing
  • headache
  • itching of the vagina or genital area
  • nonmenstrual vaginal bleeding
  • pain during sexual intercourse
  • thick, white vaginal discharge with no odor or with a mild odor
  • unusual tiredness or weakness
Incidence not known
  • Abdominal or stomach pain
  • blistering, peeling, or loosening of the skin
  • change in vaginal discharge
  • chest pain, discomfort, or tightness in chest
  • clay-colored stools
  • clear or bloody discharge from the nipple
  • confusion
  • dark urine
  • difficulty speaking
  • difficulty swallowing
  • dizziness or lightheadedness
  • double vision
  • fainting
  • fast heartbeat
  • inability to move the arms, legs, or facial muscles
  • inability to speak
  • joint or muscle pain
  • loss of appetite
  • lump in the breast or under the arm
  • nausea and vomiting
  • noisy breathing
  • pain in the ankles or knees
  • 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, red lumps under the skin, mostly on the legs
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • problems with memory or speech
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • red, irritated eyes
  • redness or swelling of the breast
  • skin rash, hives, or itching
  • sores, ulcers, or white spots in the mouth or on the lips
  • sudden shortness of breath or troubled breathing
  • sweating
  • trouble recognizing objects
  • trouble thinking and planning
  • trouble walking

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
  • Back pain
  • breast pain
  • cramps
  • crying
  • euphoria
  • mental depression
  • paranoia
  • quick to react or overreact emotionally
  • rapidly changing moods
  • trouble sleeping
  • weakness
  • weight gain
Incidence not known
  • Changes in appetite
  • changes in sexual ability, desire, drive, or performance
  • excess air or gas in the stomach or intestines
  • increased hair growth, especially on the face
  • patchy brown or dark brown discoloration of the skin
  • trouble wearing contact lenses

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%).[Ref]


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.[Ref]


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.[Ref]


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


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


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


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.


1. "Product Information. CombiPatch (estradiol-norethindrone topical)." Rhone-Poulenc Rorer, Collegeville, PA.

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

More about Ena (estradiol / norethindrone)

Consumer resources

Other brands: Mimvey, Activella, CombiPatch, Lopreeza

Professional resources

Related treatment guides

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.