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Estradiol transdermal gel

Updated 2 Feb 2023 | Oestrogens and HRT


Gel containing estradiol (as estradiol hemihydrate)

Drugs List

  • estradiol 0.06% gel
  • estradiol 0.5mg/0.5g gel
  • estradiol 1mg/1g gel
  • OESTROGEL 0.06% gel
  • SANDRENA 0.5mg/0.5g gel
  • SANDRENA 1mg/1g gel
  • Therapeutic Indications


    Replacement therapy for oestrogen deficiency symptoms
    Secondary prophylaxis of postmenopausal osteoporosis where risk of fracture



    Preparations in single dose units (Sandrena)
    The gel can be used for continuous or cyclical treatment.

    Usual starting dose 1.0 mg estradiol (equivalent to 1 g of gel) daily but is based on severity of symptoms.
    Adjust after 2 to 3 cycles according to clinical response.

    Dose range 0.5 to 1.5 mg estradiol each day (0.5 to 1.5 g of gel).

    Preparations in pressurised pump packs (Oestrogel)
    Gel should be applied continuously.

    2 measures (1.5 mg estradiol) of estradiol gel to be applied over an area twice that of the template provided once daily.

    The minimum effective dose for the prevention of osteoporosis is 1.5 mg of estradiol daily.

    If required the dosage may be increased up to a maximum of 4 measures per day (3 mg estradiol) after 1 month of therapy.

    Starting treatment (all preparations)
    Women with an intact uterus may begin treatment at any time if menstrual cycles have ceased or are infrequent.

    Women who are still menstruating should begin treatment within 5 days of the start of bleeding.

    Women with an intact uterus transferring from a sequential HRT regimen should begin treatment on the day following completion of the previous regimen


    (See Dosage; Adults)

    Additional Dosage Information

    Forgotten dose
    Apply as soon as possible unless the dose is more than 12 hours late.
    If more than 12 hours late, forget the dose and continue as normal.

    Patients should be advised not to apply two doses at the same time.

    Missed doses may increase susceptibility to breakthrough bleeding.


    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
    Lupus anticoagulant
    Myocardial infarction
    Oestrogen dependent neoplasm
    Protein C deficiency disease
    Protein S deficiency disease
    Pulmonary embolism
    Thromboembolic disorder
    Uncontrolled endometrial hyperplasia
    Undiagnosed gynaecological haemorrhage

    Precautions and Warnings

    Family history of breast cancer
    History of recurrent spontaneous abortion
    Patients over 65 years
    Predisposition to thromboembolic disease
    Prolonged immobilisation
    Recent surgery
    Recent trauma
    Severe headache
    Cardiac impairment
    Diabetes mellitus
    Endometrial hyperplasia
    Epileptic disorder
    Gall bladder disorder
    Hepatic disorder
    History of breast nodules
    History of chloasma
    History of thromboembolic disorder without anticoagulant therapy
    Malignant melanoma
    Multiple sclerosis
    Renal impairment
    Sickle cell disease
    Uterine fibroids

    Risk of pancreatitis in individuals with hypertriglyceridaemia
    Add progestogen for 12-14 days each cycle for those with an intact uterus
    Assess family medical history prior to commencing treatment
    Exclude breast cancer before treatment
    Exclude oestrogen dependent neoplasm before treatment
    Increased risk of endometrial carcinoma with unopposed oestrogens
    Not all available brands are licensed for all indications
    Some formulations contain propylene glycol
    Do not apply on or near breasts
    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 hepatic impairment
    Regular breast examination advisable
    Advise patient of thromboembolic symptoms and to report them if they occur
    Advise patient that changes in their breasts should be reported to Dr/nurse
    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 thrombophlebitis or thromboembolism
    Discontinue if abnormal neurological signs develop
    Discontinue if cerebrovascular disorders occur
    Discontinue if cholestasis develops
    Discontinue if first appearance of migraine or severe or frequent headache
    Discontinue if jaundice or other evidence of hepatic impairment occurs
    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
    Women with a history of chloasma should avoid exposure to sun/UV light

    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.

    Physical examination should be guided by this and a knowledge of the contraindications and precautions and warnings for use of the product. Investigations including mammography should be carried out in accordance with currently accepted screening practices, modified according to the clinical needs of the individual.

    There is an increased risk of breast cancer in women currently or recently using Hormone Replacement Therapy (HRT). The risk of breast cancer increases with the duration of treatment and returns to normal after 5 years of stopping treatment.

    Examinations to rule out endometrial abnormalities should be undertaken at regular intervals. Prolonged monotherapy with oestrogens increases the risk of endometrial hyperplasia and carcinoma in postmenopausal women unless supplemented by administration of a progestogen to protect the endometrium. Unless there is a previous diagnosis of endometriosis it is not recommended to add a progestogen in hysterectomised women.

    Pregnancy and Lactation


    Hormone replacement therapy is contraindicated during pregnancy.

    Should pregnancy occur, treatment should be discontinued immediately.

    Estradiol has been associated with cardiovascular defects, eye and ear abnormalities and hypospadias in the newborn when having been exposed to these in the womb (Briggs, 2011). However, some studies have failed to find a relationship with cardiovascular defects and non-genital malformations. Down's syndrome has also been associated with oestrogens as a group, but not for estradiol (Schaefer, 2007).

    Development alterations in the psychosexual performance of boys have been attributed to exposure to estradiol and progestogen in the womb. Males who have been exposed to estradiol and progestogen have demonstrated a trend to have less heterosexual characteristics and fewer masculine interests than males which have not been exposed to these hormones prenatally.

    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 ( ).


    Hormone replacement therapy is contraindicated during breastfeeding.

    Estradiol has been used to suppress postpartum breast engorgement in patients who do not desire to breastfeed (Hale, 2010). Oestrogenic agents demonstrate lower infant weight gain, decreased milk production and decreased composition of nitrogen and protein content of human milk (Briggs, 2011). Even though the extent of these changes is low, the changes in milk production and composition may be of nutritional importance in malnourished mothers. Because of the reasons mentioned above the use of this medication during lactation should be avoided.

    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


    Apply gel to clean, dry, intact areas of skin such as lower trunk, arms or thighs, using right and left sides on alternate days.

    The gel should not be applied to the breasts, vulval region, face or on irritated skin, and avoid contact with the eyes.

    The application surface should be 1 to 2 times the size of the hand, or, where the a template is provided in the pack, the size of the template. The gel should be allowed to dry for five minutes before covering with clothing.

    The application site should not be washed for at least one hour.

    Avoid skin contact with other persons (particularly male) for at least one hour.

    Advise patient of the increased risk of breast cancer vs benefits of HRT.
    Advise patient that changes in their breasts should be reported to Dr/nurse.
    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 women of child bearing potential that HRT does not provide contraceptive cover and non-hormonal contraception should be used during treatment.
    Advise patient to seek advise at first indications of pregnancy.
    Advise patient to discontinue therapy if abnormal neurological signs develop.
    Advise patient of thromboembolic symptoms and to report them if they occur (e.g. painful swelling of a leg, sudden pain in the chest, dyspnoea).
    Advise patient that the ability to drive or operate machinery may be affected by side effects.

    Side Effects

    "Spotting" bleeding
    Abdominal cramps
    Abdominal pain
    Aggravation of porphyria
    Blood lipid changes
    Breakthrough bleeding
    Breast enlargement
    Breast pain
    Breast tenderness
    Change in menstrual flow
    Changes in libido
    Cholestatic jaundice
    Deep vein thrombosis (DVT)
    Endometrial hyperplasia
    Erythema multiforme
    Erythema nodosum
    Exacerbation of epilepsy
    Exacerbation of hypocalcaemia
    Exacerbation of otosclerosis
    Exacerbation of pre-existing asthma
    Fibrocystic breast changes
    Fluid retention
    Gallbladder disease
    Increase in plasma triglyceride concentration
    Increased risk of breast cancer
    Increased risk of endometrial cancer
    Increased risk of oestrogen-dependent neoplasms
    Increased risk of ovarian cancer
    Increased size of uterine fibroids
    Intolerance to contact lenses
    Liver function disturbances
    Mood changes
    Myocardial infarction
    Premenstrual-like syndrome
    Pulmonary embolism
    Reduced carbohydrate tolerance
    Skin irritation
    Vaginal candidiasis
    Vascular purpura
    Venous thrombosis
    Weight changes

    Effects on Laboratory Tests

    Hormone replacement therapy, especially oestrogen-progestogen combined treatment may increase the density of mammographic images and adversely effect the detection of breast cancer.

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


    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 2014

    Reference Sources

    Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. Accessed on 02 October 2014.

    Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

    Summary of Product Characteristics: Sandrena 0.5 mg gel. Orion pharma UK ltd. Revised June 2018.
    Summary of Product Characteristics: Sandrena 1.0 mg gel. Orion pharma UK ltd. Revised June 2018.
    Summary of Product characteristics: Oestrogel Pump-Pack Gel. Besins Healthcare (UK) Ltd. Revised June 2019.

    The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

    MHRA Drug Safety Update September 2019
    Available at:
    Last accessed: 07 January 2020

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