Estradiol / norethindrone Side Effects
Medically reviewed by Drugs.com. Last updated on Aug 2, 2023.
Applies to estradiol / norethindrone: transdermal patch extended release. Other dosage forms:
Warning
Transdermal route (Patch, Extended Release)
Estrogens with or without progestins should not be used for the prevention of cardiovascular disease or dementia. An increased risk of DVT, pulmonary embolism, stroke, myocardial infarction, and invasive breast cancer have been reported. An increased risk of probable dementia in postmenopausal women 65 years of age or older has also been reported. There is an increased risk of endometrial cancer in women with a uterus who use unopposed estrogens. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Serious side effects
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
Other side effects
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.
General
The most common adverse events were vaginal bleeding and breast pain/tenderness. Vaginal bleeding usually occurred in the first months of treatment. Breast pain usually disappeared after a few months of therapy.[Ref]
Genitourinary
Very common (10% or more): Vaginal hemorrhage (26%), breast pain (24%), post-menopausal bleeding (11%), endometrial thickening (10%), breast tenderness, menstruation irregular
Common (1% to 10%): Ovarian cyst, uterine fibroid, breast edema, breast enlargement, uterine fibroids aggravated, uterine fibroids recurrence, uterine fibroids
Uncommon (0.1% to 1%): Endometrial hyperplasia, dysmenorrhea
Rare (less than 0.1%): Fallopian tube cysts, endocervical polyps
Postmarketing reports: Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow, breakthrough bleeding, spotting, increase in size of uterine leiomyomata, change in amount of cervical secretion, changes in cervical ectropion, pre-menstrual-like syndrome, cystitis-like syndrome, nipple discharge, galactorrhea, fibrocystic breast changes, vulvovaginal pruritus[Ref]
Nervous system
Very common (10% or more): Headache (22%)
Common (1% to 10%): Migraine or migraine aggravated, dizziness
Rare (less than 0.1%): Paresthesia
Postmarketing reports: Dizziness, exacerbation of epilepsy, dementia, chorea, stroke[Ref]
Cardiovascular
Common (1% to 10%): Blood pressure increase
Uncommon (0.1% to 1%): Thrombophlebitis superficial, venous thromboembolism
Rare (less than 0.1%): Thrombophlebitis deep, deep venous thromboembolism
Postmarketing reports: Deep and superficial vein thrombosis, thrombophlebitis, myocardial infarction, stroke, hypertension aggravated[Ref]
Gastrointestinal
Very common (10% or more): Nausea (11%)
Common (1% to 10%): Gastroenteritis, diarrhea, abdominal pain, abdominal distention, abdominal discomfort
Uncommon (0.1% to 1%): Flatulence, bloating
Postmarketing reports: Vomiting, abdominal cramps, pancreatitis, dyspepsia[Ref]
Psychiatric
Common (1% to 10%): Insomnia, emotional lability, depression or depression aggravated
Uncommon (0.1% to 1%): Nervousness, changes in libido
Postmarketing reports: Mental depression, mood disturbances, irritability, anxiety[Ref]
Other
Very common (10% or more): Accidental injury (17%)
Common (1% to 10%): Weight increase, weight decreased, edema peripheral, pain, asthenia
Uncommon (0.1% to 1%): Drug ineffective
Postmarketing reports: Fatigue, edema[Ref]
Musculoskeletal
Very common (10% or more): Back pain (10%)
Common (1% to 10%): Pain in extremity, leg cramps[Ref]
Immunologic
Very common (10% or more): Nasopharyngitis (21%), upper respiratory tract infection (18%), sinusitis (15%)
Common (1% to 10%): Infection viral, moniliasis genital, genital candidiasis or vaginitis[Ref]
Dermatologic
Common (1% to 10%): Acne, rash, pruritus, dry skin
Uncommon (0.1% to 1%): Alopecia, hirsutism, urticaria, skin reactions, skin discoloration
Postmarketing reports: Chloasma or melasma that may persist when drug is discontinued, erythema multiforme, erythema nodosum, hemorrhagic eruption, loss of scalp hair, seborrhea, skin rash, seborrhea, angioneurotic edema[Ref]
Oncologic
Uncommon (0.1% to 1%): Breast cancer
Rare (less than 0.1%): Uterine leiomyoma
Postmarketing reports: Ovarian cancer, endometrial cancer[Ref]
Hypersensitivity
Uncommon (0.1% to 1%): Hypersensitivity
Rare (less than 0.1%): Allergic reaction
Postmarketing reports: Anaphylactoid/anaphylactic reactions[Ref]
Respiratory
Rare (less than 0.1%): Pulmonary embolism, asthma
Postmarketing reports: Exacerbation of asthma[Ref]
Hepatic
Uncommon (0.1% to 1%): Gallbladder disease, gallstones, transaminases increased
Rare (less than 0.1%): Cholelithiasis
Postmarketing reports: Cholestatic jaundice, gallbladder disease, cholelithiasis aggravated, cholelithiasis recurrence[Ref]
Metabolic
Common (1% to 10%): Fluid retention
Postmarketing reports: Changes in appetite, increased triglycerides[Ref]
Ocular
Postmarketing reports: Retinal vascular thrombosis, intolerance to contact lenses, visual disturbances[Ref]
More about estradiol / norethindrone
- Check interactions
- Compare alternatives
- Pricing & coupons
- Reviews (94)
- Imprints, shape & color data
- Side effects
- Dosage information
- During pregnancy
- Drug class: sex hormone combinations
Patient resources
- Estradiol and norethindrone drug information
- Estradiol and norethindrone transdermal
- Estradiol and norethindrone (Oral) (Advanced Reading)
- Estradiol and norethindrone (Transdermal) (Advanced Reading)
- Estradiol and Norethindrone Tablets
- Estradiol and Norethindrone Patch
Other brands
CombiPatch, Activella, Mimvey, Lopreeza
Professional resources
Other brands
CombiPatch, Activella, Mimvey, Amabelz, ... +2 more
Related treatment guides
References
1. Cerner Multum, Inc. UK Summary of Product Characteristics.
2. Cerner Multum, Inc. Australian Product Information.
3. Product Information. Activella (estradiol-norethindrone). Gemini Laboratories. 2017.
4. Product Information. Lopreeza (estradiol-norethindrone). Amneal Pharmaceuticals. 2017.
5. Product Information. Mimvey (estradiol-norethindrone). Teva Pharmaceuticals USA. 2017.
6. Product Information. Amabelz (estradiol-norethindrone). Lupin Pharmaceuticals Inc. 2017.
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Some side effects may not be reported. You may report them to the FDA.