Drugs List

Therapeutic Indications

Uses

HRT for treatment of oestrogen deficiency in women with intact uterus

Hormone replacement therapy (HRT) for oestrogen deficiency symptoms in women with intact uterus who have been postmenopausal for more than 1 year.

Contraindications

Abnormal liver function test
Acute hepatic disorder
Angina
Breast cancer
Breastfeeding
Deep vein thrombosis
History of breast cancer
History of thromboembolic disorder
Hormone dependent neoplasm
Lupus anticoagulant
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
Asthma
Cholelithiasis
Diabetes mellitus
Endometrial hyperplasia
Endometriosis
Haemolytic anaemia
Hepatic adenoma
Hepatic disorder
History of chloasma
Hypertension
Hypertriglyceridaemia
Hypocalcaemia
Migraine
Otosclerosis
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
Contains propylene glycol
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
Reassess need for continued treatment at regular intervals
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
May affect results of some laboratory tests
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
Discontinue if venous thromboembolism develops
Maintain treatment at the lowest effective dose
Maintain treatment for the shortest possible duration
Female: Not for contraception.Use non-hormonal contraception, if required
Advise patient of increased risk of breast cancer vs benefits of HRT

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.

The overall evidence suggests an increased risk of breast cancer in women taking combined oestrogen-progestogen (and possibly also oestrogen-only HRT). This increased risk is dependent on the duration of HRT. The Women's Health Initiative study (WHI) and epidemiological studies have both reported an increased risk of breast cancer in women taking combined oestrogen-progestogen for HRT. This increased risk becomes apparent within 3 years of starting treatment but returns to baseline within a few (at most five) years after stopping treatment.

There is also a slightly increased risk of ovarian cancer in patients taking combined oestrogen-progesterone HRT, which becomes apparent within 5 years of therapy.

HRT is associated with up to a 3 fold risk of developing venous thromboembolism, which most often presents in the first year of therapy. In post-operative patients attention should be given to prophylactic measures to prevent VTE following surgery. Where prolonged immobilisation is liable to follow elective surgery, consideration should be given to temporarily stopping HRT 4 to 6 weeks earlier, if possible. Treatment should not be restarted until the patient is fully mobilised.

The risk of coronary artery disease is slightly increased during the use of combined oestrogen-progesterone HRT which increases with age.

The risk of ischaemic stroke is increased 1.5 fold in patients taking combined oestrogen-progesterone therapy which increases with age.

Fluid retention may be experienced in patients taking oestrogens and thus patients with cardiac or renal dysfunction should be carefully observed. Additionally, as rare cases of increased of plasma triglycerides (leading to pancreatitis) have been reported in women taking oestrogen therapy, patients with pre-existing hypertriglyceridaemia should be followed closely.

Patients who require thyroid hormone therapy should have their thyroid function monitored regularly whilst on HRT.

There is no evidence that HRT improves cognitive function. There is some evidence of increased risk of dementia in women who start using continuous combined HRT after the age of 65.

Pregnancy and Lactation

Pregnancy

Hormone replacement therapy is contraindicated during pregnancy.

Should pregnancy occur, treatment should be discontinued immediately.

At the time of writing there is limited published information regarding the use of combined estradiol-progesterone during pregnancy. Potential risks are unknown, however estradiol has been associated with cardiovascular defects, eye and ear abnormalities 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. 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 (Briggs, 2015).

Lactation

Hormone replacement therapy is contraindicated during breastfeeding.

Use of combined estradiol-progesterone when breastfeeding is contraindicated by the manufacturer. Available data indicates combined estradiol-progesterone is expressed in human breast milk, but the quantity is unknown.

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

Abdominal discomfort
Abdominal tenderness
Abnormal liver function tests
Acne
Acute pancreatitis
Adnexa uteri cyst
Agitation
Alanine aminotransferase increased
Alopecia
Anaemia
Anxiety
Arthralgia
Aspartate aminotransferase increased
Attention disturbances
Back pain
Blood pressure changes
Breast changes
Breast tenderness
Cervical changes
Chills
Chloasma
Concentration disturbances
Constipation
Coronary artery disorder
Deep vein thrombosis (DVT)
Dementia
Depression
Diarrhoea
Dizziness
Dream abnormalities
Drowsiness
Dry mouth
Dry skin
Dysgeusia
Dyspepsia
Endometrial hypertrophy
Erythema multiforme
Erythema nodosum
Fatigue
Flatulence
Fluid retention
Furuncle
Gallbladder disease
Gastro-enteritis
Headache
Hirsutism
Hyperlipidaemia
Hyperphagia
Hypersensitivity reactions
Hypertension
Hyperuricaemia
Impaired memory
Increase in alkaline phosphatase
Increased fibrinolytic activity
Increased libido
Increased partial thromboplastin time
Increased risk of breast cancer
Increased risk of ovarian cancer
Insomnia
Ischaemic stroke
Metrorrhagia
Migraine
Mood changes
Muscle spasm
Musculoskeletal pain
Nausea
Oral discomfort
Otitis media
Painful extremities
Paraesthesia
Parosmia
Pelvic pain
Postmenopausal bleeding
Prothrombin time increased
Pruritus
Pulmonary embolism
Rash
Sensory disturbances
Sleep disorders
Somnolence
Superficial vein thrombophlebitis
Telangiectasia
Uterine fibroids
Vaginal discharge
Vaginal haemorrhage
Vascular purpura
Vertigo
Visual disturbances
Vomiting
Vulvovaginal infections
Vulvovaginal itching
Weight changes

Presentation

Oral formulations of estradiol with progesterone.

Drugs List

Therapeutic Indications

Uses

HRT for treatment of oestrogen deficiency in women with intact uterus

Hormone replacement therapy (HRT) for oestrogen deficiency symptoms in women with intact uterus who have been postmenopausal for more than 1 year.

Dosage

Women should commence treatment 12 months after their last menses.

Patients who have experienced a surgically induced menopause may commence treatment immediately. Patients who are changing from a cyclical or continuous sequential preparation, should commence treatment once they have completed the 28 day cycle.

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 thromboembolic disorder
Hormone dependent neoplasm
Lupus anticoagulant
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
Asthma
Cholelithiasis
Diabetes mellitus
Endometrial hyperplasia
Endometriosis
Haemolytic anaemia
Hepatic adenoma
Hepatic disorder
History of chloasma
Hypertension
Hypertriglyceridaemia
Hypocalcaemia
Migraine
Otosclerosis
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
Contains propylene glycol
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
Reassess need for continued treatment at regular intervals
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
May affect results of some laboratory tests
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
Discontinue if venous thromboembolism develops
Maintain treatment at the lowest effective dose
Maintain treatment for the shortest possible duration
Female: Not for contraception.Use non-hormonal contraception, if required
Advise patient of increased risk of breast cancer vs benefits of HRT

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.

The overall evidence suggests an increased risk of breast cancer in women taking combined oestrogen-progestogen (and possibly also oestrogen-only HRT). This increased risk is dependent on the duration of HRT. The Women's Health Initiative study (WHI) and epidemiological studies have both reported an increased risk of breast cancer in women taking combined oestrogen-progestogen for HRT. This increased risk becomes apparent within 3 years of starting treatment but returns to baseline within a few (at most five) years after stopping treatment.

There is also a slightly increased risk of ovarian cancer in patients taking combined oestrogen-progesterone HRT, which becomes apparent within 5 years of therapy.

HRT is associated with up to a 3 fold risk of developing venous thromboembolism, which most often presents in the first year of therapy. In post-operative patients attention should be given to prophylactic measures to prevent VTE following surgery. Where prolonged immobilisation is liable to follow elective surgery, consideration should be given to temporarily stopping HRT 4 to 6 weeks earlier, if possible. Treatment should not be restarted until the patient is fully mobilised.

The risk of coronary artery disease is slightly increased during the use of combined oestrogen-progesterone HRT which increases with age.

The risk of ischaemic stroke is increased 1.5 fold in patients taking combined oestrogen-progesterone therapy which increases with age.

Fluid retention may be experienced in patients taking oestrogens and thus patients with cardiac or renal dysfunction should be carefully observed. Additionally, as rare cases of increased of plasma triglycerides (leading to pancreatitis) have been reported in women taking oestrogen therapy, patients with pre-existing hypertriglyceridaemia should be followed closely.

Patients who require thyroid hormone therapy should have their thyroid function monitored regularly whilst on HRT.

There is no evidence that HRT improves cognitive function. There is some evidence of increased risk of dementia in women who start using continuous combined HRT after the age of 65.

Pregnancy and Lactation

Pregnancy

Hormone replacement therapy is contraindicated during pregnancy.

Should pregnancy occur, treatment should be discontinued immediately.

At the time of writing there is limited published information regarding the use of combined estradiol-progesterone during pregnancy. Potential risks are unknown, however estradiol has been associated with cardiovascular defects, eye and ear abnormalities 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. 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 (Briggs, 2015).

Lactation

Hormone replacement therapy is contraindicated during breastfeeding.

Use of combined estradiol-progesterone when breastfeeding is contraindicated by the manufacturer. Available data indicates combined estradiol-progesterone is expressed in human breast milk, but the quantity is unknown.

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

Abdominal discomfort
Abdominal tenderness
Abnormal liver function tests
Acne
Acute pancreatitis
Adnexa uteri cyst
Agitation
Alanine aminotransferase increased
Alopecia
Anaemia
Anxiety
Arthralgia
Aspartate aminotransferase increased
Attention disturbances
Back pain
Blood pressure changes
Breast changes
Breast tenderness
Cervical changes
Chills
Chloasma
Concentration disturbances
Constipation
Coronary artery disorder
Deep vein thrombosis (DVT)
Dementia
Depression
Diarrhoea
Dizziness
Dream abnormalities
Drowsiness
Dry mouth
Dry skin
Dysgeusia
Dyspepsia
Endometrial hypertrophy
Erythema multiforme
Erythema nodosum
Fatigue
Flatulence
Fluid retention
Furuncle
Gallbladder disease
Gastro-enteritis
Headache
Hirsutism
Hyperlipidaemia
Hyperphagia
Hypersensitivity reactions
Hypertension
Hyperuricaemia
Impaired memory
Increase in alkaline phosphatase
Increased fibrinolytic activity
Increased libido
Increased partial thromboplastin time
Increased risk of breast cancer
Increased risk of ovarian cancer
Insomnia
Ischaemic stroke
Metrorrhagia
Migraine
Mood changes
Muscle spasm
Musculoskeletal pain
Nausea
Oral discomfort
Otitis media
Painful extremities
Paraesthesia
Parosmia
Pelvic pain
Postmenopausal bleeding
Prothrombin time increased
Pruritus
Pulmonary embolism
Rash
Sensory disturbances
Sleep disorders
Somnolence
Superficial vein thrombophlebitis
Telangiectasia
Uterine fibroids
Vaginal discharge
Vaginal haemorrhage
Vascular purpura
Vertigo
Visual disturbances
Vomiting
Vulvovaginal infections
Vulvovaginal itching
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.

Further Information

Last Full Review Date: October 2021

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: Bijuve 1mg/100mg capsules. Theramex UK Limited. Revised February 2021.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 19 October 2021

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Estradiol. Last revised: 17 March 2021
Last accessed: 19 October 2021