Combined hrt. Side effects and safety info.

What you need to know.

Helpful info to help you understand when combined HRT may not be suitable, and some of the adverse effects associated with taking it.

HRT - condition icon

Combined HRT is made up of two hormones: oestrogen and progesterone (or progestin). The oestrogen can help to tackle menopausal symptoms, like hot flushes, vaginal dryness and night sweats. On its own though, the hormone may also cause the womb to continue to grow (if you still have your womb) and this can lead to endometrial cancer.

The progesterone in combined HRT helps to manage the impact of oestrogen on the womb lining, and so restricts your cancer risk.

Combined HRT products can produce side effects however, and aren’t always suitable for everyone.


Certain side effects are fairly common with combined HRT, but they tend to ease given time, so it’s worth giving a treatment at least 3 months if you can. 

If you experience any severe side effects though, or if they persist for longer than 3 months, let our clinician know. 

Usually your prescriber will start you on the lowest dose of hormones, and any adjustments can then be made depending on how your body responds.

Serious combined HRT side effects

If you experience any of the following, you should go to hospital or see a doctor immediately.

  • Any changes to your breasts. Dimpling of the skin, changes in the nipple or any lumps you can see or feel.
  • Any signs of a blood clot. Painful swelling and redness of the legs, sudden chest pain and breathing difficulties.
  • Any yellowing of the skin or the whites of the eyes (jaundice). These can be indications of liver disease.
  • A significant rise in your blood pressure. Headache, fatigue and dizziness can be signs of this.
  • Migraine-like headaches that happen for the first time.
  • Any irregular bleeding that persists for longer than the first 6 months, or starts after you have been taking combined HRT for longer than 6 months. Or if the bleeding continues after you have stopped taking combined HRT.
  • Any sudden chest pain.
  • If you cough up blood.
  • If you become pregnant.

Side effects of oral HRT treatments

The side effects below are either very common (occur in more than 1 in 10 women) or common (may occur in up to 1 in 10 women).

  • Headache
  • Pain or tenderness in the breasts
  • Painful periods
  • Difficulties with your menstrual cycle

The following side effects may affect up to 1 in 10 women:

  • Weight gain or weight loss (caused by an increase in fluid retention)
  • Hot flushes
  • Increased sweating
  • Feeling nauseous
  • Vomiting
  • Stomach cramps
  • Vaginal discharge
  • Bleeding or spotting
  • Disorder of the vulva / vagina
  • Depression, anxiety, lack of energy
  • Mood swings
  • Dizziness
  • Changes in sex drive
  • Breast swelling
  • Swelling elsewhere in the body
  • Feeling bloated
  • Indigestion
  • Cramps in the legs
  • Acne
  • Abdominal pain
  • Back pain

Uncommon side effects (may affect up to 1 in 100 women) include:

  • Benign breast tumour, or benign growths in the lining of the womb
  • Allergic reaction
  • Increased appetite
  • High level of cholesterol in the blood
  • Difficulty sleeping
  • Reduced concentration
  • Visual impairment or dry eye
  • Higher blood pressure
  • Inflammation of a vein or varicose veins
  • Purple patches like bruising
  • Runny or blocked nose
  • Constipation / diarrhoea / rectal disorder
  • Increased frequency or urgency to pass urine
  • Gallstones and gallbladder disease
  • Breast cancer

The following side effects are considered to be rare, and may affect up to 1 in 1,000 women:

  • Changes in liver function and biliary flow
  • Skin rash
  • Blood clot, typically in a leg or lung, which results in pain, swelling or redness
  • Intolerance to contact lenses
  • Tingling or numbness
  • Growths in the womb (such as myoma, cysts and polyps)

Further side effects for which the frequency is not known may include:

  • Tumours in the uterus
  • Restricted blood supply to the brain (or to a section of the brain)
  • Hair loss
  • Eczema
  • Symptoms of hereditary angioedema worsen

The risk of developing breast cancer is thought to increase slightly amongst women using combined HRT compared to women who aren’t using it. For every 1,000 women not using combined HRT from the age of menopause up to 69 years of age, 13 may develop breast cancer. For every 1,000 women using HRT for 5 years in this same bracket, a further 10 women may develop breast cancer. 

It’s believed that there is a slightly increased risk of ovarian cancer amongst women using combined HRT too. For every 1,000 women using combined HRT over a 5 year period, there may be 1 further incidence of ovarian cancer. 

HRT tablets are also linked with a slightly higher likelihood of developing a blood clot. HRT in tablet form may produce 9 additional cases of venous thromboembolism for every 10,000 women each year. 

There’s also a small increase in your risk of developing a stroke if you use HRT. From the age of menopause up to 69 years of age, 4 women in every 1,000 may have a stroke. In this same bracket, for women who use HRT for 5 years, there may be 1 extra case of stroke. 

Side effects of topical HRT treatments

Topical HRT treatments like HRT patches contain the same hormones as oral HRT products, so a lot of the side effects are likely to be similar, although they may vary in frequency. 

There are some additional side effects that you may experience with topical HRT, however.

  • Irritated, itchy red skin (and sometimes a rash) where the patch is applied

There is no evidence of any increased breast cancer risk with topical HRT that is applied directly into the vagina. All other forms of HRT increase your risk of breast cancer slightly. 

For more information on side effects of topical combined HRT products, check the patient information leaflet that comes with your treatment.


Contraindications of oral HRT treatments

Combined continuous oral and combined sequential oral HRT products aren’t suitable for all women. 

You should not use them if:

  • you have or have ever had breast cancer, or if you are suspected of having it
  • you have (or have ever had) cancer which is sensitive to oestrogens, such as cancer of the lining of the womb (endometrium) or if you are suspected of having it
  • you have any unexplained bleeding of the vagina
  • you have any excessive thickening of the lining of the womb (endometrial hyperplasia) that isn’t being treated
  • you have or have had a blood clot in a vein (thrombosis). For example, in the legs (deep venous thrombosis) or the lungs (pulmonary embolism)
  • you have a blood clotting disorder (such as protein C, protein S, or antithrombin deficiency)
  • you have or have recently had a disease triggered by blood clots in the arteries, such as a heart attack, stroke or angina
  • you have or have ever had a liver disease, and your liver function tests aren’t normal
  • you have a rare blood problem known as ‘porphyria’, which is an inherited condition
  • you are allergic to any of the active ingredients in the treatment, or to any other ingredients in the treatment

It’s very important to let your clinician know what your medical history is during your consultation. Certain types of HRT and products may not be suitable for you if you have a medical condition. 

If you experience any of the following, you should inform your prescriber before taking any combined oral or sequential HRT treatments.

  • Fibroids inside your womb
  • Growth of the womb lining outside of your womb (endometriosis) or a history of excessive growth of the womb lining (endometrial hyperplasia)
  • Increased risk of developing blood clots
  • Increased risk of developing an oestrogen-sensitive cancer (if you have a mother, sister or grandmother who has breast cancer, for example)
  • High blood pressure
  • A liver disorder, such as a benign liver tumour
  • Diabetes
  • Gallstones
  • Migraine or severe headaches
  • A disease of the immune system that affects multiple organs in the body (systemic lupus erythematosus, SLE)
  • Epilepsy
  • Asthma
  • A very high level of fat in your blood (triglycerides)
  • Hereditary angioedema
  • Fluid retention as a result of cardiac or kidney issues
  • A disease that affects the eardrum and hearing (otosclerosis)

Contraindications of topical HRT treatments

Combined topical and combined sequential HRT treatments are made up of the same hormones as combined oral HRT products, so if combined oral HRT options are unsuitable for you due to a health condition, it’s likely that combined topical HRT products won’t be suitable for you either. 

There are some additional conditions which make combined topical treatments unsuitable for you, however. Combined topical HRT is not suitable for you if:

  • you are allergic to anything in topical HRT patches
  • you have (or have ever had) blocked arteries (arterial thrombo-embolic disease) that gave you angina or a heart attack or a stroke


Oral HRT interactions

Certain medications can interact with combined oral HRT treatments, and make them less effective. These interactions can cause irregular bleeding, and may increase your risk of developing side effects. As such, it’s very important that you let your clinician know if you have recently taken or are currently taking any other medication, or if you’ve been advised to start taking any other medication. 

If you’re getting treatment from a care provider who isn’t the prescriber providing you with combined oral HRT, it’s very important to let them know about the HRT you’re taking too (in case this impacts on your treatment).

It’s particularly important to let your prescriber know if you are taking:

  • medicines for epilepsy (such as phenobarbital, phenytoin and carbamazepine)
  • medicines for tuberculosis (such as rifampicin and rifabutin)
  • medicines for HIV infection (such as nevirapine, efavirenz, ritonavir and nelfinavir)
  • herbal remedies containing St John’s wort

Topical HRT interactions

Combined topical HRT treatments contain the same hormones as combined oral HRT products, and can cause interactions with many of the same medicines. There are a few additional medicines that combined topical HRT treatments can interact with however. 

In addition to the medicines listed above for combined oral HRT products, it’s very important that you inform your prescriber if you are taking:

  • medicine for Hepatitis C infection (telaprevir)
  • Bosentan (which treats high blood pressure in the blood vessels of the lungs)
  • St John’s wort (for depression)
  • medicine for epilepsy called lamotrigine

Before you start your EveAdam consultation, you’ll be asked to provide details of any medications you are currently using in your medical profile. It’s very important to list all of these before getting your treatment plan underway, and to ensure that you keep this updated once your plan has begun, so that our clinicians can make sure that the HRT treatment you’re using is safe for you.