Drugs List

Therapeutic Indications

Uses

Menopausal symptoms
Secondary prophylaxis of postmenopausal osteoporosis where risk of fracture

Hormone replacement therapy (HRT) to treat oestrogen deficiency symptoms in peri and postmenopausal women.

To prevent osteoporosis in postmenopausal women at high risk of fractures, who cannot take other drugs indicated for the prevention of osteoporosis. (2mg only)

Contraindications

Suspected hormone dependent neoplasm
Abnormal liver function test
Acute hepatic disorder
Angina
Antiphospholipid syndrome
Breast cancer
Breastfeeding
Deep vein thrombosis
Familial conjugated hyperbilirubinaemias
Galactosaemia
Hereditary fructose intolerance
History of breast cancer
History of hormone dependent neoplasm
History of thromboembolic disorder
History of venous thromboembolism
Hormone dependent neoplasm
Myocardial infarction
Porphyria
Pregnancy
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
History of recurrent spontaneous abortion
Patients over 65 years
Predisposition to thromboembolic disease
Prolonged immobilisation
Recent surgery
Recent trauma
Severe headache
Abnormal mammography
Asthma
Cardiac impairment
Cholelithiasis
Diabetes mellitus
Endometrial hyperplasia
Endometriosis
Epileptic disorder
Fibrocystic breast disorder
Gall bladder disorder
Glucose-galactose malabsorption syndrome
Hepatic adenoma
Hepatic disorder
History of chloasma
History of endometrial hyperplasia
History of endometriosis
Hypertension
Hypertriglyceridaemia
Hypocalcaemia
Lactose intolerance
Migraine
Multiple sclerosis
Otosclerosis
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
Not all available strengths are licensed for all indications
Contains lactose
Preparation contains sucrose
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
Advise patient to contact a doctor if symptoms of thromboembolism develop
Avoid immobilisation-treatment may cause increased risk of thromboembolism
Discontinue at the onset of severe depression
Increased risk of venous thromboembolism
Increased risk of VTE during travel involving >5hr immobilisation
May increase baseline risk of ovarian carcinoma
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 thrombophlebitis or thromboembolism
Discontinue if abnormal neurological signs develop
Discontinue if cholestasis develops
Discontinue if first occurrence or worsening of migraine/severe 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 sudden, severe pain in stomach occurs
Discontinue if symptoms due to endometriosis are exacerbated
Maintain treatment at the lowest effective dose
Maintain treatment for the shortest possible duration
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Female: Not for contraception.Use non-hormonal contraception, if required
Advise patient of increased risk of breast cancer vs benefits of HRT

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.

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 HRT. The risk of breast cancer increases with the duration of treatment and, after stopping HRT, the risk will decrease with time. When HRT lasts for more than 5 years, the risk may persist for 10 years or more.

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

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, 2015). 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, 2015).

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.

Lactation

Hormone replacement therapy is contraindicated during breastfeeding.

Oestrogenic agents demonstrate lower infant weight gain, decreased milk production and decreased composition of nitrogen and protein content of human milk (Briggs, 2015). 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.

Side Effects

"Spotting" bleeding
Abdominal pain
Acne
Aggravation of porphyria
Allergic skin reactions
Alopecia
Angioedema
Anxiety
Asthenia
Back pain
Bloating
Breakthrough bleeding
Breast enlargement
Breast pain
Breast tenderness
Cerebrovascular disorders
Cervical erosion
Change in amount of cervical secretion
Change in carbohydrate metabolism
Changes in libido
Chloasma
Cholestasis
Chorea
Coronary artery disorder
Cystitis-like syndrome
Deep vein thrombosis (DVT)
Dementia
Depression
Disturbances of appetite
Dizziness
Dysmenorrhoea
Dyspepsia
Eczema
Endometrial hyperplasia
Epistaxis
Erythema multiforme
Erythema nodosum
Exacerbation of epilepsy
Flatulence
Fluid retention
Gallbladder disease
Gastro-intestinal discomfort
Gastrointestinal disorder
Haemolytic anaemia
Haemorrhage
Haemorrhagic eruption
Headache
Hepatic disorders
Hirsutism
Hypersensitivity reactions
Hypertension
Hypertriglyceridaemia
Increase in plasma triglyceride concentration
Increased risk of breast cancer
Increased risk of endometrial cancer
Increased risk of ovarian cancer
Increased size of uterine fibroids
Intolerance to contact lenses
Jaundice
Leg pain
Malaise
Menorrhagia
Metrorrhagia
Migraine
Muscle cramps
Myocardial infarction
Nausea
Neoplasms
Oedema
Palpitations
Pancreatitis
Pelvic pain
Peripheral vascular disorders
Premenstrual-like syndrome
Pruritus
Pulmonary embolism
Rash
Steepening of corneal curvature
Stroke
Thrombophlebitis
Urticaria
Vaginal candidiasis
Vaginal discharge
Vascular purpura
Venous thrombosis
Visual disturbances
Vomiting
Weight changes

Presentation

Tablets containing estradiol valerate.

Drugs List

Therapeutic Indications

Uses

Menopausal symptoms
Secondary prophylaxis of postmenopausal osteoporosis where risk of fracture

Hormone replacement therapy (HRT) to treat oestrogen deficiency symptoms in peri and postmenopausal women.

To prevent osteoporosis in postmenopausal women at high risk of fractures, who cannot take other drugs indicated for the prevention of osteoporosis. (2mg only)

Dosage

A progestogen should be added for 12 to 14 days each cycle for women with an intact uterus, to oppose the production of an oestrogen-stimulated hyperplasia of the endometrium. It's not recommended to add a progestogen in hysterectomised women, unless there is a previous diagnosis of endometriosis.

Adults

Additional Dosage Information

Contraindications

Suspected hormone dependent neoplasm
Abnormal liver function test
Acute hepatic disorder
Angina
Antiphospholipid syndrome
Breast cancer
Breastfeeding
Deep vein thrombosis
Familial conjugated hyperbilirubinaemias
Galactosaemia
Hereditary fructose intolerance
History of breast cancer
History of hormone dependent neoplasm
History of thromboembolic disorder
History of venous thromboembolism
Hormone dependent neoplasm
Myocardial infarction
Porphyria
Pregnancy
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
History of recurrent spontaneous abortion
Patients over 65 years
Predisposition to thromboembolic disease
Prolonged immobilisation
Recent surgery
Recent trauma
Severe headache
Abnormal mammography
Asthma
Cardiac impairment
Cholelithiasis
Diabetes mellitus
Endometrial hyperplasia
Endometriosis
Epileptic disorder
Fibrocystic breast disorder
Gall bladder disorder
Glucose-galactose malabsorption syndrome
Hepatic adenoma
Hepatic disorder
History of chloasma
History of endometrial hyperplasia
History of endometriosis
Hypertension
Hypertriglyceridaemia
Hypocalcaemia
Lactose intolerance
Migraine
Multiple sclerosis
Otosclerosis
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
Not all available strengths are licensed for all indications
Contains lactose
Preparation contains sucrose
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
Advise patient to contact a doctor if symptoms of thromboembolism develop
Avoid immobilisation-treatment may cause increased risk of thromboembolism
Discontinue at the onset of severe depression
Increased risk of venous thromboembolism
Increased risk of VTE during travel involving >5hr immobilisation
May increase baseline risk of ovarian carcinoma
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 thrombophlebitis or thromboembolism
Discontinue if abnormal neurological signs develop
Discontinue if cholestasis develops
Discontinue if first occurrence or worsening of migraine/severe 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 sudden, severe pain in stomach occurs
Discontinue if symptoms due to endometriosis are exacerbated
Maintain treatment at the lowest effective dose
Maintain treatment for the shortest possible duration
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Female: Not for contraception.Use non-hormonal contraception, if required
Advise patient of increased risk of breast cancer vs benefits of HRT

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.

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 HRT. The risk of breast cancer increases with the duration of treatment and, after stopping HRT, the risk will decrease with time. When HRT lasts for more than 5 years, the risk may persist for 10 years or more.

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

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, 2015). 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, 2015).

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.

Lactation

Hormone replacement therapy is contraindicated during breastfeeding.

Oestrogenic agents demonstrate lower infant weight gain, decreased milk production and decreased composition of nitrogen and protein content of human milk (Briggs, 2015). 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.

Side Effects

"Spotting" bleeding
Abdominal pain
Acne
Aggravation of porphyria
Allergic skin reactions
Alopecia
Angioedema
Anxiety
Asthenia
Back pain
Bloating
Breakthrough bleeding
Breast enlargement
Breast pain
Breast tenderness
Cerebrovascular disorders
Cervical erosion
Change in amount of cervical secretion
Change in carbohydrate metabolism
Changes in libido
Chloasma
Cholestasis
Chorea
Coronary artery disorder
Cystitis-like syndrome
Deep vein thrombosis (DVT)
Dementia
Depression
Disturbances of appetite
Dizziness
Dysmenorrhoea
Dyspepsia
Eczema
Endometrial hyperplasia
Epistaxis
Erythema multiforme
Erythema nodosum
Exacerbation of epilepsy
Flatulence
Fluid retention
Gallbladder disease
Gastro-intestinal discomfort
Gastrointestinal disorder
Haemolytic anaemia
Haemorrhage
Haemorrhagic eruption
Headache
Hepatic disorders
Hirsutism
Hypersensitivity reactions
Hypertension
Hypertriglyceridaemia
Increase in plasma triglyceride concentration
Increased risk of breast cancer
Increased risk of endometrial cancer
Increased risk of ovarian cancer
Increased size of uterine fibroids
Intolerance to contact lenses
Jaundice
Leg pain
Malaise
Menorrhagia
Metrorrhagia
Migraine
Muscle cramps
Myocardial infarction
Nausea
Neoplasms
Oedema
Palpitations
Pancreatitis
Pelvic pain
Peripheral vascular disorders
Premenstrual-like syndrome
Pruritus
Pulmonary embolism
Rash
Steepening of corneal curvature
Stroke
Thrombophlebitis
Urticaria
Vaginal candidiasis
Vaginal discharge
Vascular purpura
Venous thrombosis
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 affect the detection of breast cancer.

The use of oestrogen may influence laboratory test 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: August 2022.

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

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: Progynova tablets 1mg. Bayer plc. Revised June 2022

Summary of product characteristics: Progynova tablets 2mg. Bayer plc. Revised June 2022

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 18 August 2022