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Estradiol vaginal


Vaginal tablets containing estradiol.

Drugs List

  • estradiol 10microgram pessary
  • GINA 10microgram vaginal tablets
  • VAGIFEM 10microgram vaginal tablets
  • VAGIRUX 10microgram vaginal tablets
  • Therapeutic Indications


    Atrophic vaginitis - post-menopausal


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


    Initial dose: One vaginal tablet daily for two weeks. Maintenance dose: One vaginal tablet twice a week. Treatment may be started on any convenient day.


    Abnormal liver function test
    Acute hepatic disorder
    Antiphospholipid syndrome
    Breast cancer
    Deep vein thrombosis
    History of breast cancer
    History of hormone dependent neoplasm
    History of thromboembolic disorder
    History of venous thromboembolism
    Hormone dependent neoplasm
    Myocardial infarction
    Pulmonary embolism
    Recent arterial thromboembolic disorder
    Thromboembolic disorder
    Thrombophilic disorder
    Uncontrolled endometrial hyperplasia
    Undiagnosed gynaecological haemorrhage

    Precautions and Warnings

    Family history of breast cancer
    Hereditary angioedema
    Patients over 65 years
    Predisposition to thromboembolic disease
    Prolonged immobilisation
    Risk factor for oestrogen-dependent neoplasm
    Severe headache
    Cardiac impairment
    Diabetes mellitus
    Endometrial hyperplasia
    Epileptic disorder
    Hepatic adenoma
    Hepatic disorder
    History of chloasma
    Renal impairment
    Systemic lupus erythematosus
    Uterine fibroids

    Risk of pancreatitis in individuals with hypertriglyceridaemia
    Assess family medical history prior to commencing treatment
    Exclude breast cancer before treatment
    Exclude oestrogen dependent neoplasm before treatment
    Treat vaginal infections before initiation of therapy
    Do breast & pelvic exam. before & during treatment if clinically indicated
    Follow up at least annually with physical and gynaecological examination
    Investigate persistent or recurrent vaginal bleeding
    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
    Advise patients to report gynaecological bleeding and/or pelvic pain
    Increased risk of VTE during travel involving >5hr immobilisation
    May increase baseline risk of ovarian carcinoma
    Prolonged use of unopposed oestrogen may incr.risk of endometrial carcinoma
    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 first occurrence or worsening of migraine/severe headache
    Discontinue if hepatic function deteriorates
    Discontinue if jaundice or other evidence of hepatic impairment occurs
    Discontinue if significant rise in blood pressure occurs
    Discontinue if symptoms due to endometriosis are exacerbated
    Advise patient not to take St John's wort concurrently
    Advise patient of increased risk of breast cancer vs benefits of HRT
    Advise patients risk of endometrial cancer and to report relevant symptoms

    Hormone replacement therapy should only be initiated in patients with symptoms that adversely affect quality of life. Careful consideration of the risks and benefits should be undertaken at least annually and HRT should only be continued as long as the benefits outweigh the risks.

    Medical examinations which include appropriate imaging tools, e.g. mammography, should be carried out in accordance with current screening practices and modified to the needs of the individual.

    Women should be examined with special care if they have an intact uterus with undiagnosed abnormal bleeding or women with an intact uterus who have previously been treated with unopposed oestrogens. This is in order to exclude hyperstimulation/malignancy of the endometrium before treatment initiation. There is very little systemic absorption of estradiol during treatment with estradiol vaginal tablets, however, being a HRT product, the following need to be considered, especially in repeated or long term use.

    The risk of endometrial hyperplasia and carcinoma is increased when oestrogens are administered alone for prolonged periods of time in women with an intact uterus. As the systemic exposure to oestrogen is within normal postmenopausal range, it is not recommended to add a progestogen with oestrogen products for vaginal application. Endometrial safety of repeated or long term (more than one year) use of vaginally administered oestrogen is uncertain. Therefore, if repeated, it is recommended that treatment is reviewed at least annually. Special consideration should be given to any symptoms of endometrial hyperplasia or carcinoma.

    Evidence suggest there is no increased risk of breast cancer in women with no history of breast cancer taking low dose vaginally applied oestrogens. It is unknown if low dose vaginal oestrogens stimulate a recurrence of breast cancer. In hysterectomised women using oestrogen only HRT, the WHI trial found no increase in risk of breast cancer.

    An association has been made between long-term (at least 5 to 10 years) use of oestrogen only HRT products and a slightly increased risk of ovarian cancer. The long term use of oestrogen-progesterone combined HRT may confer a similar or slightly smaller risk.

    HRT is associated with a 1.3 to 3 fold risk of developing venous thromboembolism (VTE), which is more likely in the first year of HRT than later. In women who have no personal history of VTE, but have a first degree relative with a history of VTE at a young age screening may be offered. The woman should be carefully counselled with regards to the screenings limitations. This should include the information that only a proportion of thrombophilic defects are identified by screening.

    There is a 1.5 fold increase in risk of ischaemic stroke in women taking combined HRT and oestrogen only HRT. It should be noted that the relative risk does not change with age or time since menopause but as the baseline risk of stroke is strongly age dependent, the overall risk of stroke in women who use HRT increase with age.

    Oestrogens increase thyroid binding globulin (TBG), leading to increased circulating total thyroid hormone, T4 levels or T3 levels. T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Other binding proteins may be elevated in serum i.e. corticoid binding globulin and sex hormone binding globulin leading to increased circulating corticosteroids and sex steroids, respectively. Free or biologically active hormone concentrations are unchanged. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha 1 antitrypsin, ceruloplasmin). Vaginal administration of estradiol is associated with minimal systemic absorption and thus is less likely to have pronounced effects on plasma binding proteins than systemic HRT.

    There is some evidence of an increased risk of probable dementia in women who start using continuous combined or oestrogen only HRT after the age of 65. In women with serious vaginal atrophy, the intravaginal applicator may cause minor local trauma.

    Pregnancy and Lactation


    Estradiol is contraindicated during pregnancy.

    The manufacturer does not recommend using estradiol during pregnancy. Should pregnancy occur, treatment should be discontinued immediately. The results of most epidemiological studies to date indicate no teratogenic or foetotoxic effects.
    In some studies estradiol has been associated with cardiovascular defects and hypospadias in the newborn when having been exposed to estradiol in utero. However, other studies have failed to find a relationship with cardiovascular defects and non-genital malformations (Briggs, 2015).

    Development alterations in the psychosexual performance of boys have been attributed to exposure to estradiol and progestogen in the womb. Males which 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 (Briggs, 2015).


    Estradiol is contraindicated during breastfeeding.

    The manufacturer does not recommend estradiol during breastfeeding.

    Estradiol has been used to suppress postpartum breast engorgement in patients who do not desire to breast feed. In women receiving 50 or 100 mg of vaginal estradiol, less than 10% of the dose was expressed in breast milk. The American Academy of Paediatrics classifies estradiol as compatible with breastfeeding (Briggs, 2015).


    If a dose is forgotten it should be taken as soon as the patient remembers. A double dose should be avoided.

    Advise patient not to take St John's wort concurrently.

    Advise patients risk of endometrial cancer and to report relevant symptoms.

    Advise patient of thromboembolic symptoms and to report them if they occur.

    Advise patient to report gynaecological bleeding.

    Advise patient to examine their breast(s) regularly and report any changes to their doctor or nurse immediately, due to the risk of breast cancer.

    Advise patient to seek advise at the first indications of pregnancy.

    Advise patient to participate in the national breast cancer and cervical cancer screening programmes as appropriate for their age.

    Advise patient of increased risk of breast cancer versus benefits of treatment.

    Side Effects

    Abdominal pain
    Anaphylactic reaction
    Anaphylactic shock
    Breast pain
    Deep vein thrombosis (DVT)
    Endometrial hyperplasia
    Erythema multiforme
    Erythema nodosum
    Erythematous rash
    Fluid retention
    Gallbladder disease
    Hot flushes
    Hypersensitivity reactions
    Increased risk of breast cancer
    Peripheral oedema
    Postmenopausal bleeding
    Risk of endometrial carcinoma
    Slight vaginal bleeding
    Vaginal candidiasis
    Vaginal discharge
    Vaginal discomfort
    Vaginal haemorrhage
    Vaginal irritation
    Vaginal pain
    Vaginal ulcers
    Vascular purpura
    Vulvovaginal infections
    Weight gain

    Effects on Laboratory Tests

    Combined oestrogen and progesterone HRT preparations may increase the density of mammographic images which may adversely effect the 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: November 2020

    Reference Sources

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

    Summary of Product Characteristics: Gina 10 micrograms vaginal tablets. Novo Nordisk Limited. Revised June 2022.

    Summary of Product Characteristics: Vagifem 10mcg vaginal tablets. Novo Nordisk Limited. Revised September 2018.

    Summary of Product Characteristics: Vagirux 10mcg vaginal tablets. Gedeon Rickter (UK) Limited. Revised August 2020.

    NICE Evidence Services Available at: Last accessed: 17 October 2022

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