Estradiol and Norethindrone (Transdermal)

Estradiol and norethindrone transdermal patches are used to control some of the symptoms experienced by menopausal women and is also used to treat poor estrogen levels in pre-menopausal patients.


In the US, estradiol and norethindrone transdermal patches are sold under the brand name Combipatch. In Canada, the drug is branded as Estalis and Estalis-Sequi.

Estradiol and norethindrone patches are used to treat menopausal symptoms, including hot flashes, vaginal dryness, burning, and itching. The drug is also effective in tackling low estrogen levels in pre-menopausal women whose ovaries do not naturally produce enough estrogen. Estradiol and norethindrone combines two female hormones; estradiol (estrogen hormone) and norethindrone (progestin hormone). The body absorbs both hormones through the skin.

The drug works by balancing hormone levels in the body, preventing symptoms such as sudden, strong feelings of heat, warmth in the neck, face, and chest (hot flashes), and night sweats.

The medication is available only via prescription from your GP and comes in extended-release, transdermal patch form.

Conditions treated

  • Menopausal symptoms
  • Low estrogen levels

Type of medicine

  • Hormone therapy
  • Transdermal, extended-release patches

Side effects

Some medication can cause unwanted side effects in addition to the effects it is designed to produce. Not everyone using estradiol and norethindrone patches will experience any side effects, but you should mention them to your doctor if you do.

If any of the following side effects do occur, contact your doctor straight away:

  • Jaundice
  • Vomiting of blood
  • Vaginal bleeding
  • Unusual weight gain or loss
  • Unusual tiredness or weakness
  • Unpleasant breath odor
  • Trouble swallowing or breathing
  • Tingling of the feet or hands
  • Tightness of the chest
  • Thick, white vaginal discharge, with or without odor
  • Swelling of the face, eyelids, face, lips, feet, or hands
  • Sores on the breast skin that will not heal
  • Slow or rapid heartbeat
  • Severe cramping of the uterus
  • Swelling or redness of the breast
  • Redness of the skin
  • Recurrent fever
  • Rash
  • Pounding in the ears
  • Persistent crusting or scaling of the nipple
  • Painful or difficult urination
  • Pain or feeling of pressure in the pelvis
  • Pain during sexual intercourse
  • Nervousness
  • Nausea and vomiting
  • Lump in the breast or under the arm
  • Lower back or side pain
  • Loss of appetite
  • Large hives on the face, lips, eyelids, tongue, hands, throat, legs, genitals, or feet
  • Joint pain, stiffness, or swelling
  • Itching of the genital area
  • Itching
  • Irritation
  • Inverted nipple
  • Hoarseness
  • Hives
  • Heavy vaginal bleeding
  • Severe, throbbing headache
  • Gaseous abdominal or stomach pain
  • Fever or chills
  • Dizziness
  • Dimpling of the breast skin
  • Diarrhea
  • Dark urine
  • Clear or bloody discharge from the nipple
  • Clay-colored stools
  • Change in vaginal discharge
  • Blurred vision
  • Abdominal or stomach bloating or feeling of fullness

There are some side effects caused by estradiol and norethindrone that may not necessarily need further medical advice. These effects often disappear without further treatment once you have been using the patches for a month or two. Ask your doctor for advice on how to manage any effects that prove to be especially inconvenient or persistent, or if you have any further questions about your treatment.

  • Weight gain
  • Insomnia
  • Problems concentrating
  • Tiredness
  • Thick, white vaginal discharge
  • Tender, swollen glands in the neck
  • Sweating
  • Stuffy or runny nose
  • Stomach discomfort or upset
  • Sneezing
  • Shivering
  • Sensation of spinning
  • Pimples
  • Passing gas
  • Pain or tenderness around the cheekbones and eyes
  • Pain during sexual intercourse
  • Muscle stiffness, aches, and pains
  • Loss of interest or pleasure
  • Low libido
  • Longer or heavier menstrual periods
  • Lack or loss of strength
  • Irritability
  • Indigestion
  • Increased interest in sexual intercourse
  • Heavy vaginal bleeding
  • Heartburn
  • Headache
  • General feeling of discomfort or illness
  • Feeling sad or empty
  • Feeling of constant movement of self or surroundings
  • Excess air or gas in the stomach or intestines
  • Dull ache or feeling of pressure or heaviness in the legs
  • Dryness or soreness of the throat
  • Dizziness or lightheadedness
  • Discouragement
  • Difficulty with moving
  • Constipation
  • Cramps
  • Congestion
  • Change in color of the treated skin
  • Skin irritation at the patch application site
  • Feelings of burning, itching, crawling, numbness, "pins and needles", prickling, or tingling
  • Breast pain
  • Body aches or pain
  • Skin blemishes
  • Belching
  • Back pain
  • Acid or sour stomach

It should be noted that this list may not be exhaustive. If you notice any other odd effects that are not included in this guide, you should discuss them with your treating physician as soon as possible.


You must only use estradiol and norethindrone patches exactly as instructed by your treating physician. Do not use the patches more often or for a longer period of time than you have been told to. If you deviate from your doctor's instructions, you could increase the risk of suffering unwanted side effects.

Your prescription of estradiol and norethindrone patches will come with a patient information leaflet, which you should read fully. If you have any questions about your patches, ask your pharmacist or doctor.

Before beginning treatment with CombiPatch®, you will need to tell your GP if you are already using estrogen or estrogen in combination with progestin. Your doctor will need this information in order to work out when your treatment should commence. Some patients may note a small amount of light monthly bleeding or spotting when each cycle of the drug is complete.

Transdermal patches should be applied to your skin, in the lower stomach area, top of the thighs, or on the upper buttocks, twice weekly, depending on your dosage regimen and as advised by your doctor. Do not apply the patches to any other area of your body or the medicine will not be as effective.

Using estradiol and norethindrone skin patches

  • Make sure that your hands are clean and dry before using this medication.
  • The patches are supplied in protective patches. Remove the patch from the pouch when you are ready to use it. Do not cut the patch.
  • Remove the peel-off backing from the patch. Apply the patch to a clean, blemish-free site. Avoid areas that are hairy or scarred. Do not apply body lotion, powder or oils before using the patch as this will stop it sticking to the skin.
  • Gently press down on the patch for a few seconds, until it sticks.
  • Keep the patch on until it is time to renew it. Do not remove the patch when showering or bathing, and do not expose it to direct sunlight.
  • Between applications of new patches, allow sufficient time for the skin to settle before using the same site.
  • Gently peel the old patch from your skin. Allow any remaining adhesive to dry for 15 minutes or so, and then rub it gently until it comes away.
  • Try to change the patch on the same day of the week, so that you do not forget.
  • If the patch comes off, replace it in a different place. If the old patch will not stick properly, remove it and use a fresh one. However, you should continue to follow your original schedule for renewing patches.
  • When you remove an old patch, fold it in half with sticky sides facing each other. Place the old patch in a bag, seal it, and put it into the trash well away from children and animals. Do not flush the patches down the toilet.

Dosage rates

The recommended dose for this medication will vary between patients. You should follow your doctor's directions or the instructions on the product label. The information contained here is based on the average only for this drug. If your dose is not the same as this, do not alter it unless you are told to by your treating physician.

The frequency of use of the patches and their strength will depend on your condition and also on the strength of the preparation that you have been prescribed.

To treat atrophic vaginitis and hot flashes caused by the menopause 'continuous combined regimen:

  • Adults: 1 patch should be applied twice weekly at three to four-day intervals over a 28-day cycle.
  • Children: It is not recommended to use estradiol and norethindrone patches for children.

To treat atrophic vaginitis and hot flashes caused by the menopause ' continuous sequential combined regimen:

  • Adults: Apply one 0.05 mg estradiol patch twice weekly at three to four-day intervals for the first two weeks of the 28-day cycle. Next, apply one CombiPatch® twice weekly, every three to four days for 14 days of the 28-day cycle.
  • Children: It is not recommended to use estradiol and norethindrone patches for children.

In order for the drug to work correctly and provide continuous relief from the symptoms of menopause, there must be a constant level of both its constituent hormones in your body. If you omit to change one or your patches or if you forget to put one on, you should apply one as soon as you can. If it is nearly time to change your patch, miss out the one you omitted and apply a fresh one on the usual day. Do not apply additional patches. Only wear one patch at a time.

In the event that you accidentally overdose, remove the extra patches as soon as you can. If you experience breathing problems or lose consciousness, call 911 immediately.

These patches are not designed for oral use and may be harmful if chewed or swallowed. If someone in your household does chew or eat a patch, contact your doctor immediately.

Do not stop using the patches without first consulting your doctor. If you are told to stop using them, you will be instructed to do so gradually.


Some medicines should not be used together, as doing so could cause an interaction to take place. In other cases, it may be applicable to use both drugs at the same time, although your doctor may change the dose or frequency of use of one or both of the medicines.

While you are using estradiol and norethindrone patches, you must tell your GP if you are using any of the medication mentioned in the list below. These medicines can all cause interactions that could be undesirable. If you do need to take any of these medicines, your doctor will probably change the dose of one or both products and may also tell you to stop taking one of them.

  • Ulipristal
  • Tranexamic Acid
  • Tizanidine
  • Theophylline
  • Sugammadex
  • Pixantrone
  • Pitolisant
  • Lumacaftor
  • Lixisenatide
  • Lesinurad
  • Isotretinoin
  • Idelalisib
  • Eliglustat
  • Donepezil
  • Darunavir
  • Dabrafenib
  • Conivaptan
  • Ceritinib
  • Carbamazepine
  • Bupropion

Taking any of the medications listed below while using estradiol and norethindrone patches can present an increased danger of some side effects occurring. However, your doctor may decide that using both medicines together is the best course of action, albeit with an adjusted dose rate.

  • Warfarin
  • Voriconazole
  • Valdecoxib
  • Troleandomycin
  • Troglitazone
  • Topiramate
  • Tipranavir
  • Telaprevir
  • Tacrine
  • St John's Wort
  • Selegiline
  • Rufinamide
  • Rosuvastatin
  • Ritonavir
  • Rifapentine
  • Rifampin
  • Rifabutin
  • Primidone
  • Prednisolone
  • Phenytoin
  • Phenobarbital
  • Parecoxib
  • Oxcarbazepine
  • Nelfinavir
  • Mycophenolic Acid
  • Mycophenolate Mofetil
  • Modafinil
  • Licorice
  • Levothyroxine
  • Lamotrigine
  • Ketoconazole
  • Griseofulvin
  • Ginseng
  • Fosphenytoin
  • Fosaprepitant
  • Fosamprenavir
  • Etravirine
  • Efavirenz
  • Delavirdine
  • Cyclosporine
  • Colesevelam
  • Clarithromycin
  • Bosentan
  • Bexarotene
  • Betamethasone
  • Bacampicillin
  • Atazanavir
  • Aprepitant
  • Amprenavir
  • Alprazolam

Some drugs can cause an interaction to occur if they are used at the same time as eating certain foods, drinking alcohol, or using tobacco. In the case of estradiol and norethindrone patches, consuming caffeine can cause an increased risk of some side effects. Try to avoid eating products such as chocolate and drinking excessive amounts of coffee and cola, unless they are decaf varieties. Talk to your doctor for more information on this aspect of your treatment with this medication.

You should not eat grapefruit or drink grapefruit juice while you are using estradiol and norethindrone patches. Grapefruit and grapefruit juice can alter the amount of the drug that your body absorbs.

Medical history

Some existing and historical medical conditions can affect how this medication works. You must discuss your medical history in full with your doctor before you begin using estradiol and norethindrone patches.

Note that estradiol and norethindrone patches should not be used in patients who have a history of any of the following illnesses:

  • Known or suspected estrogen-dependent tumors
  • Stroke
  • Protein c, protein s, or other known blood clotting disorders
  • Liver disease
  • Heart attack
  • Known or suspected breast cancer
  • Blood clots (eg, deep vein thrombosis, pulmonary embolism)
  • Abnormal or unusual vaginal bleeding

Estradiol and norethindrone patches should be used with caution in patients with a history of any of the following conditions, as doing so could make these conditions worse:

This medication must be used with caution in people who have a medical history that includes any of the conditions listed below. Estradiol and norethindrone can cause serious side effects and interactions with these conditions:

  • Prolonged periods of immobilization
  • Obesity
  • Hypertriglyceridemia (high triglycerides or fats in the blood)
  • Hypertension (high blood pressure)
  • Hypercholesterolemia (high cholesterol or fats in the blood)
  • Heart disease


When deciding to use any drug, you should consider the risks versus the benefits of doing so. This decision should be taken based on discussions that you will have with your GP.

Before starting to use estradiol and norethindrone patches, you should mention to your GP any unusual or strange reactions that you have experienced to this drug or to any other prescription or over the counter medicines. Be sure to include vitamin and herbal preparations in your discussion and mention any allergies that you have to food colors, preservatives, animal derivatives, or particular food groups.


It is not appropriate to use CombiPatch® in children.

Geriatric patients

There are no specific studies into the effects of using CombiPatch® in elderly people. However, geriatric patients are more likely to be affected by dementia, stroke, or breast cancer, meaning that extra caution should be taken in people using this drug.

Pregnancy and breastfeeding

Studies that have been carried out in pregnant women have shown that using estradiol and norethindrone during all trimesters of pregnancy can cause fetal abnormalities. You should not use this medication if you are pregnant or if you are likely to become pregnant. Be sure to use an effective form of contraception while you are using estradiol and norethindrone patches. This advice may not be applicable to post-menopausal women, but you should still discuss the matter with your doctor.

It has not been shown that estradiol and norethindrone passes into breast milk or that it could present a risk to a nursing infant. However, you may wish to discuss this with your doctor or midwife and consider using an alternative method of feeding your child while you are using estradiol and norethindrone.

Medical complications

You must attend your GP regularly for progress checks while you are using this medication. These updates should usually take place once every year. They allow your doctor to make sure that the drug is working as desired and that it is not causing any unwanted side effects. You may be required to undergo a mammogram (breast X-ray), pelvic exam, or breast exam during the course of your treatment. Make sure that you keep all your scheduled appointments. In the meantime, if you notice any lumps in your breast or under your armpits, contact your doctor immediately.

Using estradiol and norethindrone can sometimes present an increased risk of strokes, heart attacks, and blood clots in some patients. You should be aware that this risk may still be present, even once you have stopped using the medication. The risk of these complications is higher in patients who have high blood pressure, diabetes, high blood cholesterol, are overweight, or who smoke tobacco products. If you experience any of the following symptoms while you are using estradiol and norethindrone, you should speak to your doctor straight away:

  • Paralysis of your arms, legs or facial muscles
  • Inability to speak
  • Headaches
  • Double vision
  • Difficulty speaking
  • Confusion
  • Chest pain

Using estradiol and norethindrone can increase the risk of certain forms of cancer, including breast cancer, uterine cancer, or endometrial cancer. You should discuss this risk with your GP and ask for advice immediately if you notice any abnormal bleeding from your vagina.

You must not use estradiol and norethindrone if you have had a hysterectomy (womb removal).

Note that using estradiol and norethindrone can present an increased risk of certain patients developing dementia, especially if they are aged 65 years or more.

If you experience sudden severe headaches, loss of vision, or any other visual disturbances or changes while you are using this medication, you must tell your doctor. You may be referred to an ophthalmologist (eye specialist) in this case to have your eyes checked.

Using estradiol and norethindrone can cause several serious allergic reactions in some susceptible patients. If you experience any of the following symptoms, you may be suffering from anaphylaxis:

  • Trouble swallowing
  • Trouble breathing
  • Swelling of your hands, face, or mouth
  • Lightheadedness or dizziness
  • Itching
  • Hoarseness
  • A rash

In this event, you should call 911 immediately.

Note that you may need to stop using this medication if you are due to have surgery or if you need to remain confined to bed for any length of time. Estradiol and norethindrone can also affect certain medical test results, so be sure to tell your doctor or dentist if appropriate.

You must not take any other medication while using estradiol and norethindrone patches unless your GP has told you that you can. This includes both over the counter and prescription medicines, herbal and vitamin preparations.

Never share your medication with anyone else.


Store your estradiol and norethindrone patches somewhere out of direct sunlight and away from sources of heat and moisture. Keep all the patches in their original pouches until you are ready to use one. Your prescription of transdermal patches should be good for up to six months, provided they are kept at room temperature.

Keep your medication well away from children and pets. This drug can be dangerous if consumed orally. If a pet eats one of your patches, contact your emergency vet immediately.

Dispose of used patches responsibly and safely. Fold the patch in half, sticky side in. Place the patch in a bag, seal it, and put it into the bottom of your trash can. Do not flush used patches down the toilet.


Estradiol and norethindrone transdermal skin patches are used to treat common symptoms that are experienced by menopausal women. They are also used to correct low estrogen levels in pre-menopausal women whose bodies do not naturally produce sufficient amounts of estrogen. The active hormones contained in the medicine are absorbed from the patches through the patient's skin over an extended period, thus ensuring that constant levels are maintained in the user's body. Your doctor will prescribe you this medication for use until your body has gone through the menopause and the troublesome symptoms naturally cease.

Women who are pre-menopausal should note that estradiol and norethindrone can present a danger to the fetus. Pregnancy is therefore not advised and you should tell your doctor if you decide that you wish to become pregnant while you are still using this drug.

Throughout the course of your treatment with estradiol and norethindrone you must attend your GP or practice nurse for regular reviews to make sure that the medication is working properly and that you are not experiencing any bothersome side effects. Certain tests may be required as part of this process. You should be aware that using this drug can increase your risk of breast cancer. Be sure to examine yourself for signs of lumps either in your breasts or under your armpits, and mention anything unusual to your doctor right away.

This medication should not be used with certain other drugs and foodstuffs. It can also cause complications in patients who have a history of certain health conditions. For these reasons you must discuss your medical history fully with your doctor before you begin using estradiol and norethindrone patches.