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Estradiol with (estradiol and norethisterone) oral

Updated 2 Feb 2023 | Oestrogens and HRT


Tablets containing estradiol 2mg
Tablets containing estradiol 2mg and norethisterone 1mg

Drugs List

  • CLINORETTE tablets
  • estradiol 2mg tablets and estradiol 2mg with norethisterone 1mg tablets
  • Therapeutic Indications


    HRT for treatment of oestrogen deficiency in women with intact uterus
    Secondary prophylaxis of postmenopausal osteoporosis where risk of fracture


    For initiation and continuation of treatment, the lowest effective dose for the shortest duration should be used.


    One estradiol tablet to be taken daily for the first 16 days, followed by one estradiol with norethisterone combined tablet daily for the next 12 days. The next 28 day cycle should then commence without a break.

    Treatment is continuous, so when one course is finished the next should be started the next day without an interval. A menstrual-type vaginal bleed usually occurs at the end of the treatment cycle or after administration of the last estradiol and norethisterone tablet.

    Starting treatment:

    In women who are still menstruating, the first tablet should be taken on the fifth day of bleeding.

    Patients who are not menstruating, or in whom bleeding is infrequent or sporadic, may take the first tablet at any time.

    Patients changing from a cyclic or continuous sequential HRT preparation should complete the cycle and then start treatment without a break in therapy.

    Patients changing from a continuous combined HRT preparation may begin therapy at any time if amenorrhoea is established or otherwise start on the first day of bleeding.


    (See Dosage; Adults)

    Additional Dosage Information

    Missed or forgotten tablets should be taken as soon as is convenient. However if a whole day has passed the missed tablet should be discarded and the next tablet taken at the usual time. A missed dose may increase the likelihood of breakthrough bleeding and spotting.

    Breakthrough bleeding may occasionally occur in the first few weeks after initiating treatment but will usually settle.


    Suspected hormone dependent neoplasm
    Abnormal liver function test
    Acute hepatic disorder
    Breast cancer
    Deep vein thrombosis
    Familial conjugated hyperbilirubinaemias
    History of breast cancer
    History of hormone dependent neoplasm
    History of thromboembolic disorder without anticoagulant therapy
    History of venous thromboembolism
    Protein C deficiency disease
    Protein S deficiency disease
    Recent arterial thromboembolic disorder
    Thromboembolic disorder
    Uncontrolled endometrial hyperplasia
    Undiagnosed gynaecological haemorrhage

    Precautions and Warnings

    Body mass index above 30kg per square metre
    Family history of breast cancer
    Family history of venous thromboembolism
    History of recurrent spontaneous abortion
    Patients over 65 years
    Predisposition to thromboembolic disease
    Prolonged immobilisation
    Recent surgery
    Recent trauma
    Severe headache
    Abnormal mammography
    Cardiac impairment
    Diabetes mellitus
    Endometrial hyperplasia
    Epileptic disorder
    Familial hypertriglyceridaemia
    Fibrocystic breast disorder
    Gall bladder disorder
    Glucose-galactose malabsorption syndrome
    Hepatic disorder
    Hepatic impairment
    History of chloasma
    History of endometrial hyperplasia
    History of endometriosis
    History of jaundice
    History of thromboembolic disorder
    Lactose intolerance
    Malignant melanoma
    Multiple sclerosis
    Renal impairment
    Sickle cell disease
    Systemic lupus erythematosus
    Uterine fibroids

    Assess family medical history prior to commencing treatment
    Not all available brands are licensed for all indications
    Contains lactose
    Do breast & pelvic exam. before & during treatment if clinically indicated
    Exclude pregnancy prior to initiation of treatment
    Abnormal and/or irregular bleeding should be investigated
    Advise patients of risks/benefits & review need for treatment regularly
    Discontinue treatment if patient develops seizures
    Monitor hepatic function in patients with history of hepatic disease
    Advise patient that changes in their breasts should be reported to Dr/nurse
    Advise patient to contact a doctor if symptoms of thromboembolism develop
    Discontinue at the onset of severe depression
    Increased risk of VTE during travel involving >5hr immobilisation
    May interfere with certain laboratory measurements
    Discontinue 4 - 6 weeks before major surgery
    Advise patient to seek advice at first indications of pregnancy
    Discontinue at first signs of jaundice
    Discontinue at first signs of thrombophlebitis or thromboembolism
    Discontinue if cerebrovascular disorders occur
    Discontinue if cholestasis develops
    Discontinue if first occurrence or worsening of migraine/severe headache
    Discontinue if first occurrence or worsening of visual disturbances
    Discontinue if pre-existing uterine fibroids increase in size
    Discontinue if significant rise in blood pressure occurs
    Discontinue if sudden pain in the chest occurs
    Discontinue if symptoms due to endometriosis are exacerbated
    Advise patient not to take St John's wort concurrently
    Female: Not for contraception.Use non-hormonal contraception, if required
    Advise patient of increased risk of breast cancer vs benefits of HRT

    Hormone replace therapy (HRT) should only be initiated for postmenopausal symptoms that adversely affect quality of life. A careful appraisal of the benefits and risks should be undertaken at least annually and treatment should only be continued as long as the benefit outweighs the risk.

    For the treatment of menopausal symptoms the benefits of short-term HRT are considered to outweigh the risks in the majority of women.
    In all cases, it is good practice to use the lowest effective dose for the shortest possible time and to review the need to continue treatment at least annually.
    For postmenopausal women over 50 years who are at an increased risk of bone fracture, HRT should be used to prevent osteoporosis only in those who are intolerant of, or contraindicated for, other osteoporosis therapies.

    Pregnancy and Lactation


    Contraindicated during pregnancy.

    Stop treatment immediately if pregnancy is suspected.

    Data on a limited number of exposed pregnancies indicate adverse effects of norethisterone on the foetus. At higher doses than those used for HRT, masculisation of female foetuses has been observed. The results of most epidemiological studies to date relevant to foetal exposure to combinations of oestrogens with progestogens, indicate no teratogenic or foetotoxic effects.

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( ) or if this is unavailable at the backup site ( ).


    Contraindicated in breastfeeding.

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at


    Encourage patients to participate in the national breast cancer screening programme and the national cervical cancer screening programme as appropriate for their age. Breast awareness should also be encouraged and patients advised to report any changes in their breasts to their doctor or nurse

    Advise patients to contact their doctor if they are aware of a potential thromboembolic symptom (e.g. painful swelling of a leg, sudden pain in the chest, dyspnoea).

    Stop treatment immediately if pregnancy is suspected.

    Side Effects

    "Spotting" bleeding
    Abdominal cramps
    Abdominal pain
    Aggravation of porphyria
    Allergic skin reactions
    Back pain
    Breakthrough bleeding
    Breast enlargement
    Breast pain
    Breast tenderness
    Cervical erosion
    Change in amount of cervical secretion
    Change in carbohydrate metabolism
    Changes in libido
    Cholestatic jaundice
    Cystitis-like syndrome
    Deep vein thrombosis (DVT)
    Endometrial hyperplasia
    Erythema multiforme
    Erythema nodosum
    Exacerbation of epilepsy
    Exacerbation of varicose veins
    Fluid retention
    Gallbladder disease
    Haemorrhagic eruption
    Hypersensitivity reactions
    Increase in plasma triglyceride concentration
    Increased risk of breast cancer
    Increased risk of endometrial cancer
    Increased risk of ovarian cancer
    Increased size of uterine fibroids
    Intolerance to contact lenses
    Leg cramps
    Liver function disturbances
    Myocardial infarction
    Pelvic pain
    Peripheral oedema
    Peripheral vascular disorders
    Premenstrual-like syndrome
    Pulmonary embolism
    Sodium retention
    Steepening of corneal curvature
    Thromboembolic disorders
    Vaginal candidiasis
    Vascular purpura
    Weight changes

    Effects on Laboratory Tests

    The use of oestrogen may influence the laboratory results of certain endocrine tests and liver enzymes.

    HRT increases the density of mammographic images and may adversely affect the radiological detection of breast cancer.


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: October 2013

    Reference Sources

    Summary of Product Characteristics: Clinorette - Estradiol 2mg / Norethisterone 1mg tablets. Resource Medical UK Ltd. March 2013.

    NICE Evidence Services Available at: Last accessed: 06 December 2022

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