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Estradiol hemihydrate vaginal ring


Vaginal ring containing estradiol.

Drugs List

  • estradiol 7.5microgram/24hour vaginal ring
  • ESTRING 7.5microgram/24hour vaginal delivery system
  • Therapeutic Indications


    Atrophic vaginitis - post-menopausal



    One ring to be inserted and to be worn continuously for 90 days. After 90 days the ring may be replaced as appropriate.

    Each vaginal ring delivers approximately 7.5 micrograms of estradiol hemihydrate every 24 hours for a duration of 90 days.

    The maximum recommended duration of continuous therapy is 2 years.

    Treatment may start at any time in women with amenorrhoea or in those who have long intervals between menstruation.

    Additional Dosage Information

    Estradiol vaginal ring is local therapy and the addition of a progestogen for women with an intact uterus is not necessary.

    The dose of estradiol is insufficient to treat systemic vasomotor symptoms postmenopausal symptoms, or for prevention of osteoporosis.

    Patients changing from cyclical or continuous sequential HRT preparations should complete this cycle and estradiol hemihydrate vaginal ring may be introduced after a withdrawal bleed. Therapy may start at any time in patients who are changing from a continuous combined preparation.


    For vaginal administration.

    Insertion of the vaginal ring
    A relaxed position must be found.
    Open the fold of skin around the vagina.
    Press the ring into an oval shape.
    Push the ring into the vagina as far as it will go. It should be directed upwards and backwards towards the small of the back.

    Removal of the vaginal ring
    Place a finger into the vagina and hook this around the ring.
    Gently pull the ring downwards and forwards.


    Predisposition to thromboembolic disease
    Abnormal liver function test
    Acute hepatic disorder
    Breast cancer
    History of breast cancer
    History of thromboembolic disorder
    Hormone dependent neoplasm
    Ischaemic heart disease
    Uncontrolled endometrial hyperplasia
    Undiagnosed gynaecological haemorrhage
    Venous thromboembolism

    Precautions and Warnings

    Family history of breast cancer
    Hereditary angioedema
    Predisposition to venous thromboembolism
    Risk factors for cardiovascular disorder
    Severe headache
    Cardiac impairment
    Diabetes mellitus
    Epileptic disorder
    Hepatic adenoma
    Hepatic disorder
    History of endometrial hyperplasia
    Renal impairment
    Systemic lupus erythematosus
    Uterine fibroids
    Vaginal infection
    Vaginal ulceration

    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
    Adherence to vaginal wall and difficult ring removal can occur
    Do breast & pelvic exam. before & during treatment if clinically indicated
    Advise patients of risks/benefits & review need for treatment regularly
    If upper abdominal complaints/liver enlargement consider liver tumour
    Investigate if abnormal vaginal bleeding, pain or discharge occurs
    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
    Avoid immobilisation-treatment may cause increased risk of thromboembolism
    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 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
    Advise patient not to take St John's wort concurrently
    Female: Not for contraception.Use non-hormonal contraception, if required

    The pharmacokinetic profile of estradiol hemihydrate vaginal ring shows that there is low systemic absorption of estradiol and that plasma level remain at post-menopausal levels, However, as estradiol vaginal ring is a HRT product, precautions, warnings and side effects related with high systemic absorption of estradiol should still be considered.

    Hormone replacement therapy (HRT) should only be considered for patients whose symptoms adversely affect quality of life. An annual careful appraisal of the risks and benefits should be undertaken.

    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.

    Assessment of each woman before taking hormone replacement therapy (and at regular intervals thereafter) should include a personal and family medical history.

    Physical examination should be guided by this and a knowledge of the contraindications and precautions and warnings for use of the product.

    Clinical examination of pelvis and breast should be performed where clinically indicated rather than as a routine procedure.

    Investigations including mammography and cervical cytology should be carried out in accordance with currently accepted screening practices, modified according to the clinical needs of the individual.

    Some women may be unsuitable for treatment with estradiol vaginal ring, in particular those with short narrow vaginas due to previous surgery or the effect of atrophy, or those with a degree of uterovaginal prolapse severe enough to prevent retention of the ring.

    Any woman with symptoms/signs of abnormal vaginal discharge, vaginal discomfort, or any vaginal bleeding should be examined fully, to exclude ulceration, infection, or unresponsive atrophic vaginitis. Minor signs of irritation are often transient.

    Any woman experiencing persistent or severe discomfort due to the presence of the ring or excessive movement of the ring should be withdrawn from treatment. Patient with signs of ulceration or severe inflammation due to unresponsive atrophic vaginitis should also be withdrawn from treatment.

    Adherence to vaginal wall and difficult ring removal can occur. Some cases have required surgical removal.

    Patients with vaginal infection should be treated appropriately. In the case of systemic therapy, estradiol vaginal ring treatment may continue without interruption. However, removal of the ring should be considered while using other vaginal preparations.

    There have been incidences of both the ring falling out and movement of the ring, generally at defecation. Therefore, if the woman is constipated she should remove the ring before defecation. There may also be other instances when some women wish to remove the ring, e.g. prior to sexual intercourse.

    Patients on long-term corticosteroid treatment or those with conditions causing poor skin integrity, e.g. Cushing's Disease, may be unsuitable for treatment as they may have vaginal atrophy unresponsive oestrogen therapy.

    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. The increased risk of endometrial cancer, among systemic oestrogen only users, varies from 2 to 12 fold compared with non-users. This is dependant on both duration of treatment and on oestrogen dose. The risk may remain elevated for at least 10 years after withdrawing treatment.

    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.

    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.

    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.

    Pregnancy and Lactation


    Hormone replacement therapy is contraindicated during pregnancy.

    Should pregnancy occur, treatment should be discontinued immediately.

    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.

    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

    Side Effects

    Abdominal discomfort
    Abdominal pain
    Bladder pain
    General pruritus
    Genital pruritus
    Hypersensitivity reactions
    Rectal discomfort
    Sensation of pressure
    Urinary tract infections
    Vaginal adhesion
    Vaginal erosion
    Vaginal ulceration
    Vulvovaginal discomfort
    Vulvovaginal infections


    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 2018

    Reference Sources

    Summary of Product Characteristics: Estring. Pfizer Ltd. Revised June 2018.

    NICE Evidence Services Available at: Last accessed: 05 November 2018

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