Drugs List

Therapeutic Indications

Uses

Hormone replacement therapy for the treatment of the climacteric syndrome
Secondary prophylaxis of postmenopausal osteoporosis where risk of fracture

Contraindications

Major surgery with prolonged post-operative immobilisation
Abnormal liver function test
Angina
Breast cancer
Breastfeeding
Deep vein thrombosis
Galactosaemia
History of breast cancer
History of hormone dependent neoplasm
History of thromboembolic disorder
Myocardial infarction
Oestrogen dependent neoplasm
Porphyria
Pregnancy
Pulmonary embolism
Thromboembolic disorder
Thrombophilia
Uncontrolled endometrial hyperplasia
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Body mass index above 30kg per square metre
History of recurrent spontaneous abortion
Patients over 65 years
Predisposition to thromboembolic disease
Risk factor for oestrogen-dependent neoplasm
Severe trauma
Asthma
Cardiac impairment
Cholelithiasis
Diabetes mellitus
Endometriosis
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hepatic adenoma
Hereditary angioneurotic oedema
History of endometrial hyperplasia
Hypertension
Hypertriglyceridaemia
Hypophyseal neoplasm
Hypothyroidism
Lactose intolerance
Migraine
Otosclerosis
Renal impairment
Systemic lupus erythematosus
Uterine fibroids

Patients on thyroid replacement therapy may require increased doses
Assess family medical history prior to commencing treatment
Exclude breast cancer before treatment
Exclude oestrogen dependent neoplasm before treatment
Not all available strengths are licensed for all indications
Contains lactose
Some brands contain Sunset Yellow (E110) - can trigger allergic reactions
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
Monitor blood glucose closely in patients with diabetes mellitus
Women with hypertriglyceridaemia need special surveillance
Advise patient that changes in their breasts should be reported to Dr/nurse
Advise patient to contact a doctor if symptoms of thromboembolism develop
May affect results of some laboratory tests
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 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 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

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

Pregnancy

Estradiol with (estradiol and norethisterone acetate) is contraindicated in pregnancy.

Should pregnancy occur, treatment should be discontinued immediately.

Norethisterone has been associated with masculinisation of the female foetus, with one researcher observing an 18% incidence of masculinisation of female infants born to mothers given norethisterone. However, a more conservative estimate of the incidence of masculinisation was reported as 0.3%. 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. Both estradiol and norethisterone have been associated with cardiovascular defects, eye and ear abnormalities and hypospadias in the newborn when having been exposed to these in the womb. 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.

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

Lactation

Estradiol with (estradiol and norethisterone acetate) is contraindicated in breastfeeding.

Estradiol has been used to suppress postpartum breast engorgement in patients who do not desire to breast feed. Norethisterone also suppresses lactation, but produces a dose-dependent suppression. Both norethisterone and oestrogenic agents demonstrate lower infant weight gain, decreased milk production and decreased composition of nitrogen and protein content of human milk. 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.

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

Side Effects

Abdominal pain
Acne
Alopecia
Anxiety
Bloating
Blood lipid changes
Breakthrough bleeding
Breast enlargement
Breast tenderness
Change in menstrual flow
Changes in libido
Chloasma
Cholestatic jaundice
Dementia
Depression
Diarrhoea
Dizziness
Dysmenorrhoea
Dyspepsia
Endometrial hyperplasia
Endometrial neoplasia
Erythema multiforme
Erythema nodosum
Flatulence
Fluid retention
Gallbladder disease
Gallstones
General pruritus
Haemorrhagic eruption
Headache
Hirsutism
Hypersensitivity reactions
Hypertension
Increased risk of breast cancer
Increased size of uterine fibroids
Insomnia
Intolerance to contact lenses
Leg cramps
Migraine
Mood changes
Muscle cramps
Myocardial infarction
Nausea
Nervousness
Oedema
Pancreatitis
Premenstrual-like syndrome
Rash
Reduced carbohydrate tolerance
Risk of endometrial carcinoma
Sodium retention
Stroke
Thrombophlebitis
Vaginal candidiasis
Vaginal haemorrhage
Vascular purpura
Venous thrombosis
Vertigo
Vomiting
Weight changes

Presentation

Tablets containing estradiol hemihydrate and tablets containing estradiol hemihydrate with norethisterone acetate

Drugs List

Therapeutic Indications

Uses

Hormone replacement therapy for the treatment of the climacteric syndrome
Secondary prophylaxis of postmenopausal osteoporosis where risk of fracture

Dosage

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

Patients who have undergone a hysterectomy do not require the addition of progestogen to the treatment regimen and should use an oestrogen only preparation unless there is a previous diagnosis of endometriosis.

Adults

Elderly

Additional Dosage Information

Contraindications

Major surgery with prolonged post-operative immobilisation
Abnormal liver function test
Angina
Breast cancer
Breastfeeding
Deep vein thrombosis
Galactosaemia
History of breast cancer
History of hormone dependent neoplasm
History of thromboembolic disorder
Myocardial infarction
Oestrogen dependent neoplasm
Porphyria
Pregnancy
Pulmonary embolism
Thromboembolic disorder
Thrombophilia
Uncontrolled endometrial hyperplasia
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Body mass index above 30kg per square metre
History of recurrent spontaneous abortion
Patients over 65 years
Predisposition to thromboembolic disease
Risk factor for oestrogen-dependent neoplasm
Severe trauma
Asthma
Cardiac impairment
Cholelithiasis
Diabetes mellitus
Endometriosis
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hepatic adenoma
Hereditary angioneurotic oedema
History of endometrial hyperplasia
Hypertension
Hypertriglyceridaemia
Hypophyseal neoplasm
Hypothyroidism
Lactose intolerance
Migraine
Otosclerosis
Renal impairment
Systemic lupus erythematosus
Uterine fibroids

Patients on thyroid replacement therapy may require increased doses
Assess family medical history prior to commencing treatment
Exclude breast cancer before treatment
Exclude oestrogen dependent neoplasm before treatment
Not all available strengths are licensed for all indications
Contains lactose
Some brands contain Sunset Yellow (E110) - can trigger allergic reactions
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
Monitor blood glucose closely in patients with diabetes mellitus
Women with hypertriglyceridaemia need special surveillance
Advise patient that changes in their breasts should be reported to Dr/nurse
Advise patient to contact a doctor if symptoms of thromboembolism develop
May affect results of some laboratory tests
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 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 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

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

Pregnancy

Estradiol with (estradiol and norethisterone acetate) is contraindicated in pregnancy.

Should pregnancy occur, treatment should be discontinued immediately.

Norethisterone has been associated with masculinisation of the female foetus, with one researcher observing an 18% incidence of masculinisation of female infants born to mothers given norethisterone. However, a more conservative estimate of the incidence of masculinisation was reported as 0.3%. 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. Both estradiol and norethisterone have been associated with cardiovascular defects, eye and ear abnormalities and hypospadias in the newborn when having been exposed to these in the womb. 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.

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

Lactation

Estradiol with (estradiol and norethisterone acetate) is contraindicated in breastfeeding.

Estradiol has been used to suppress postpartum breast engorgement in patients who do not desire to breast feed. Norethisterone also suppresses lactation, but produces a dose-dependent suppression. Both norethisterone and oestrogenic agents demonstrate lower infant weight gain, decreased milk production and decreased composition of nitrogen and protein content of human milk. 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.

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

Counselling

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).

Advise patient not to take St John's Wort, as this may induce the metabolism of oestrogens and progestogens.

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

Side Effects

Abdominal pain
Acne
Alopecia
Anxiety
Bloating
Blood lipid changes
Breakthrough bleeding
Breast enlargement
Breast tenderness
Change in menstrual flow
Changes in libido
Chloasma
Cholestatic jaundice
Dementia
Depression
Diarrhoea
Dizziness
Dysmenorrhoea
Dyspepsia
Endometrial hyperplasia
Endometrial neoplasia
Erythema multiforme
Erythema nodosum
Flatulence
Fluid retention
Gallbladder disease
Gallstones
General pruritus
Haemorrhagic eruption
Headache
Hirsutism
Hypersensitivity reactions
Hypertension
Increased risk of breast cancer
Increased size of uterine fibroids
Insomnia
Intolerance to contact lenses
Leg cramps
Migraine
Mood changes
Muscle cramps
Myocardial infarction
Nausea
Nervousness
Oedema
Pancreatitis
Premenstrual-like syndrome
Rash
Reduced carbohydrate tolerance
Risk of endometrial carcinoma
Sodium retention
Stroke
Thrombophlebitis
Vaginal candidiasis
Vaginal haemorrhage
Vascular purpura
Venous thrombosis
Vertigo
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 liver 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: April 2016

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. 71st ed. London: BMJ Group and Pharmaceutical Press; 2016.

Summary of Product Characteristics: Elleste Duet 1mg. Meda Pharmaceuticals. Revised October 2015.

Summary of Product Characteristics: Elleste Duet 2mg. Meda Pharmaceuticals. Revised October 2015.

Summary of Product Characteristics: Novofem film-coated tablets. Novo Nordisk Ltd. Revised November 2015.