Drugs List

Therapeutic Indications

Uses

Replacement therapy for oestrogen deficiency symptoms

Hormone replacement therapy (HRT) for oestrogen deficiency symptoms in postmenopausal women (in women at least 6 months since last menses or surgical menopause with or without uterus).

Contraindications

Abnormal liver function test
Acute hepatic disorder
Angina
Breast cancer
Breastfeeding
Deep vein thrombosis
History of breast cancer
History of hormone dependent neoplasm
History of thromboembolic disorder
Hormone dependent neoplasm
Myocardial infarction
Porphyria
Pregnancy
Pulmonary embolism
Thromboembolic disorder
Thrombophilic disorder
Uncontrolled endometrial hyperplasia
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Family history of breast cancer
Patients over 65 years
Predisposition to thromboembolic disease
Prolonged immobilisation
Recent surgery
Recent trauma
Severe headache
Abnormal mammography
Asthma
Cardiac impairment
Cholelithiasis
Diabetes mellitus
Endometriosis
Epileptic disorder
Hepatic adenoma
Hepatic disorder
Hereditary angioneurotic oedema
History of chloasma
History of endometrial hyperplasia
History of endometriosis
Hypertension
Hypertriglyceridaemia
Migraine
Otosclerosis
Renal impairment
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
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 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 at the onset of severe depression
Increased risk of VTE during travel involving >5hr immobilisation
Uterine fibroids may increase in size
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 cholestasis develops
Discontinue if first appearance of migraine or severe or frequent headache
Discontinue if first occurrence or worsening of visual disturbances
Discontinue if headache with sudden partial/complete vision loss occurs
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if liver function deteriorates
Discontinue if significant rise in blood pressure occurs
Discontinue if sudden pain in the chest occurs
Discontinue if sudden, severe pain in stomach 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 patient to avoid exposure of application site for at least 1 hour
Advise patient to avoid washing application site for at least 1 hour
Use of sunscreen within 1 hour of application may reduce drug absorption

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. When carrying out initial medical examinations of patients, ensure that investigations (including appropriate imaging tools, e.g. mammography) are carried out in accordance with currently accepted screening practices.

During the first months of treatment, break-through bleeding and spotting may occur. If break-through bleeding or spotting appears after the first few months, or continues after treatment has been discontinued, the reason should be investigated. This may include endometrial biopsy to exclude endometrial malignancy.

Studies have shown an increased risk of developing breast cancer in women taking oestrogen-progesterone HRT, which usually becomes apparent after 3 years of therapy. The risk of breast cancer returns to normal after about 5 years of stopping treatment.

Evidence suggests a slight increased risk of ovarian cancer in women taking oestrogen-only or combined oestrogen and progestogen HRT, which becomes apparent within 5 years of use and diminishes over time after stopping.

HRT is associated with a 1.3 to 3 fold risk of developing venous thromboembolism. The occurrence of such an event is most likely during the first year of HRT.

There is a 1.5 fold increase in risk of ischaemic stroke in patients receiving combined oestrogen-progestogen and oestrogen-only therapy. The relative risk does not change with age or time since menopause.

In women who start using continuous combined or oestrogen-only HRT after the age of 65, some studies have shown an increased risk of probable dementia.

There is a 1.5 fold increase in risk of ischaemic stroke in patients receiving combined oestrogen-progestogen and oestrogen-only therapy. The relative risk does not change with age or time since menopause.

Avoid contact of the treated area with children, if contact has been made, soap and water should be used to wash the contacted area.

Avoid contact of the treated area with pets, a veterinarian should be contacted if pets exhibits mammary/nipple enlargement and/or vulvar swelling.

Pregnancy and Lactation

Pregnancy

Estradiol is contraindicated during pregnancy.

The manufacturer advises that treatment should be withdrawn immediately if pregnancy occurs. Studies associated with inadvertent foetal exposure to oestrogens indicate no teratogenic or foetoxic effect.

Lactation

Estradiol is contraindicated during breastfeeding.

The manufacturer does not recommend the use of estradiol spray during breastfeeding.

Side Effects

"Spotting" bleeding
Abdominal pain
Acne
Alopecia
Anxiety
Axillary pain
Bloating
Breast enlargement
Breast pain
Breast tenderness
Cervical polyp
Changes in libido
Chloasma
Depression
Diarrhoea
Dizziness
Dysmenorrhoea
Dyspepsia
Endometrial hyperplasia
Erythema nodosum
Fatigue
Gamma glutamyl transferase (GGT) increased
Headache
Hirsutism
Hypercholesterolaemia
Hypertension
Insomnia
Intolerance to contact lenses
Metrorrhagia
Migraine
Muscle spasm
Myalgia
Nausea
Oedema
Ovarian cysts
Palpitations
Premenstrual-like syndrome
Pruritus
Rash
Skin discolouration
Skin irritation
Urticaria
Vaginal bleeding
Vaginitis
Vertigo
Visual disturbances
Vomiting
Weight changes

Presentation

Transdermal spray containing estradiol.

Drugs List

Therapeutic Indications

Uses

Replacement therapy for oestrogen deficiency symptoms

Hormone replacement therapy (HRT) for oestrogen deficiency symptoms in postmenopausal women (in women at least 6 months since last menses or surgical menopause with or without uterus).

Dosage

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

Adults

Additional Dosage Information

Contraindications

Abnormal liver function test
Acute hepatic disorder
Angina
Breast cancer
Breastfeeding
Deep vein thrombosis
History of breast cancer
History of hormone dependent neoplasm
History of thromboembolic disorder
Hormone dependent neoplasm
Myocardial infarction
Porphyria
Pregnancy
Pulmonary embolism
Thromboembolic disorder
Thrombophilic disorder
Uncontrolled endometrial hyperplasia
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Family history of breast cancer
Patients over 65 years
Predisposition to thromboembolic disease
Prolonged immobilisation
Recent surgery
Recent trauma
Severe headache
Abnormal mammography
Asthma
Cardiac impairment
Cholelithiasis
Diabetes mellitus
Endometriosis
Epileptic disorder
Hepatic adenoma
Hepatic disorder
Hereditary angioneurotic oedema
History of chloasma
History of endometrial hyperplasia
History of endometriosis
Hypertension
Hypertriglyceridaemia
Migraine
Otosclerosis
Renal impairment
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
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 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 at the onset of severe depression
Increased risk of VTE during travel involving >5hr immobilisation
Uterine fibroids may increase in size
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 cholestasis develops
Discontinue if first appearance of migraine or severe or frequent headache
Discontinue if first occurrence or worsening of visual disturbances
Discontinue if headache with sudden partial/complete vision loss occurs
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if liver function deteriorates
Discontinue if significant rise in blood pressure occurs
Discontinue if sudden pain in the chest occurs
Discontinue if sudden, severe pain in stomach 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 patient to avoid exposure of application site for at least 1 hour
Advise patient to avoid washing application site for at least 1 hour
Use of sunscreen within 1 hour of application may reduce drug absorption

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. When carrying out initial medical examinations of patients, ensure that investigations (including appropriate imaging tools, e.g. mammography) are carried out in accordance with currently accepted screening practices.

During the first months of treatment, break-through bleeding and spotting may occur. If break-through bleeding or spotting appears after the first few months, or continues after treatment has been discontinued, the reason should be investigated. This may include endometrial biopsy to exclude endometrial malignancy.

Studies have shown an increased risk of developing breast cancer in women taking oestrogen-progesterone HRT, which usually becomes apparent after 3 years of therapy. The risk of breast cancer returns to normal after about 5 years of stopping treatment.

Evidence suggests a slight increased risk of ovarian cancer in women taking oestrogen-only or combined oestrogen and progestogen HRT, which becomes apparent within 5 years of use and diminishes over time after stopping.

HRT is associated with a 1.3 to 3 fold risk of developing venous thromboembolism. The occurrence of such an event is most likely during the first year of HRT.

There is a 1.5 fold increase in risk of ischaemic stroke in patients receiving combined oestrogen-progestogen and oestrogen-only therapy. The relative risk does not change with age or time since menopause.

In women who start using continuous combined or oestrogen-only HRT after the age of 65, some studies have shown an increased risk of probable dementia.

There is a 1.5 fold increase in risk of ischaemic stroke in patients receiving combined oestrogen-progestogen and oestrogen-only therapy. The relative risk does not change with age or time since menopause.

Avoid contact of the treated area with children, if contact has been made, soap and water should be used to wash the contacted area.

Avoid contact of the treated area with pets, a veterinarian should be contacted if pets exhibits mammary/nipple enlargement and/or vulvar swelling.

Pregnancy and Lactation

Pregnancy

Estradiol is contraindicated during pregnancy.

The manufacturer advises that treatment should be withdrawn immediately if pregnancy occurs. Studies associated with inadvertent foetal exposure to oestrogens indicate no teratogenic or foetoxic effect.

Lactation

Estradiol is contraindicated during breastfeeding.

The manufacturer does not recommend the use of estradiol spray during breastfeeding.

Counselling

The container should be held upright and vertical for spraying and before its first use the applicator should be primed by spraying three times into the cover.

Advise patient to use estradiol transdermal spray with caution in extreme temperature conditions such as sun bathing or sauna.

Advise patient to avoid washing application site for at least 1 hour after dose.

Advise patient to avoid exposure of application site for at least 1 hour after dose.

Advise patient to discontinue treatment and consult their doctor if they suspect pregnancy.

Advise patients not to self-medicate with St John's Wort during treatment with HRT.

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).

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.

Side Effects

"Spotting" bleeding
Abdominal pain
Acne
Alopecia
Anxiety
Axillary pain
Bloating
Breast enlargement
Breast pain
Breast tenderness
Cervical polyp
Changes in libido
Chloasma
Depression
Diarrhoea
Dizziness
Dysmenorrhoea
Dyspepsia
Endometrial hyperplasia
Erythema nodosum
Fatigue
Gamma glutamyl transferase (GGT) increased
Headache
Hirsutism
Hypercholesterolaemia
Hypertension
Insomnia
Intolerance to contact lenses
Metrorrhagia
Migraine
Muscle spasm
Myalgia
Nausea
Oedema
Ovarian cysts
Palpitations
Premenstrual-like syndrome
Pruritus
Rash
Skin discolouration
Skin irritation
Urticaria
Vaginal bleeding
Vaginitis
Vertigo
Visual disturbances
Vomiting
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 their enzymes.

Overdosage

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 ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: May 2020

Reference Sources

Summary of Product Characteristics: Lenzetto 1.53 mg/spray, transdermal spray, solution. Geodeon Rickter (UK) Ltd. Revised September 2022.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 12 May 2020