Estradiol Valerate

Estradiol Valerate tablet is indicated in Hormone replacement therapy (HRT) for estrogen deficiency symptoms in peri- and postmenopausal women. It is used for the prevention of osteoporosis in postmenopausal women at high risk of future fracture.

Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. Increases in the down-stream effects of Estrogen Receptor binding reverses some of the symptoms of menopause, which are primarily caused by a loss of estrogenic activity.

Absorption: After oral administration estradiol valerate is quickly and completely absorbed.

Metabolism: Exogenous estrogens are metabolized using the same mechanism as endogenous estrogens. Estrogens are partially metabolized by cytochrome P450.

Excretion: Estradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates.

Estradiol Valerate is an estrogen-only product. 1 mg tablet to be taken daily. It does not matter at what time of day the woman takes her tablet, but once she has selected a particular time she should keep to it every day. Treatment is continuous, which means that the next pack follows immediately without a break.

For initiation and continuation of treatment of menopausal symptoms, the lowest effective dose for the shortest duration should be used. Treatment to control menopausal symptoms should be initiated with Estradiol Valerate 1 mg tablet. If considered necessary, Estradiol Valerate 2 mg should be used. Once treatment is established the lowest effective does necessary for relief of symptoms should be used.

In women with an intact uterus, a progestogen should be added to Estradiol Valerate 1 mg for at least 12-14 days each month/28 day cycle. Unless there is a previous diagnosis of endometriosis, it is not recommended to add a progestogen in hysterectomised women.

How to start Estradiol Valerate 1 mg: If the woman has an intact uterus and is still menstruating, a combination regimen with Valest and a progestogen, commencing with the oestrogen phase, should begin on the first day of bleeding. If the menstrual periods are very infrequent or if amenorrhoea is established, she may start at any time provided, if appropriate, pregnancy has been excluded.

In women transferring from a continuous combined HRT product, treatment with Estradiol Valerate may be started on any day. In women transferring from cyclic or continuous sequential HRT regimens the woman should complete the cycle and then change to without a break in therapy.

Missed or lost tablets: If the woman forgets to take a tablet at the usual time, she may take it within the following 12 hours. If the woman is more than 12 hours late the forgotten tablet should not be taken and the remaining tablets taken at the usual time on the right days. A missed dose may lead to breakthrough bleeding or spotting.

Pediatric population: Not recommended for children

Method of administration: The tablets can be taken with or without food. The tablets should be swallowed whole with a glass of water or milk. The tablets should be taken at the same time each day.

• Known, past or suspected breast cancer
• Known or suspected oestrogen-dependent malignant tumours e.g. endometrial cancer
• Undiagnosed genital bleeding
• Untreated endometrial hyperplasia
• Previous idiopathic or current venous thromboembolism (deep venous thrombosis, pulmonary embolism)
• Known thrombophilic disorders (e.g. protein C, protein S, or antithrombin deficiency)
• Active or recent
• arterialthromboembolic disease e.g. angina, myocardial infarction
• Acute liver disease, or a history of liver disease as long as liver function tests have failed to return to normal
• Hypersensitivity to the active substances or to any of the excipients
• Porphyria

The following diseases are reported more often in women using HRT compared to women not using HRT:

• breast cancer
• abnormal growth or cancer of the lining of the womb (endometrial hyperplasia or cancer)
• ovarian cancer
• blood clots in the veins of the legs or lungs (venous thromboembolism)
• heart disease
• stroke
• probable memory loss if HRT is started over the age of 65 Other side effects that have been linked to the use of Estradiol Valerate and other oral hormone replacement therapies
• During the first few months of treatment you may experience some vaginal bleeding at unexpected times (breakthrough bleeding and spotting). These symptoms normally lessen with continued treatment. If they don’t, contact your doctor (see section 2 HRT and cancer/Excessive thickening of the lining of the womb (endometrial hyperplasia) and cancer of the lining of the womb (endometrial cancer)’ for more information)
• breast pain, tenderness or enlargement, breast discharge
• painful periods, changes in vaginal secretions, pre-menstrual symptoms, increased size of fibroids in the womb, thrush, changes to the neck of the womb
• indigestion, a feeling of being bloated, passing wind, feeling or being sick, abdominal pain, gall bladder disease
• skin rashes or discolouration, itching, eczema, acne, unusual hair loss or hair growth, increased skin pigment especially on the face (chloasma other conditions for more information), some rare skin problems
• headache, migraine, dizziness, anxiety or depressive symptoms, fatigue
• fast or irregular heartbeat (palpitations), high blood pressure, inflammation of veins usually in the legs
• fluid retention leading to swelling of parts of the body
• changes in body weight and sex drive, increased appetite
• muscle cramps, leg pains
• nose bleeds, visual disturbances (such as blurred vision), discomfort with contact lenses, allergic-type reactions, a worsening of glucose tolerance, bladder inflammation, rare disorders (porphyria, chorea).

It is not indicated during pregnancy. If pregnancy occurs during medication with it treatment should be withdrawn immediately. The results of most epidemiological studies to date relevant to inadvertent foetal exposure to oestrogens indicate no teratogenic or foetotoxic effects. This is not indicated during breast-feeding.

For the treatment of postmenopausal symptoms, HRT should only be initiated for symptoms that adversely affect quality of life. In all cases, a careful appraisal of the risk and benefits should be undertaken at least annually and HRT should only be continued as long as the benefit outweighs the risk.

Evidence regarding the risks associated with HRT in the treatment of premature menopause is limited. Due to the low level of absolute risk in younger women, however, the balance of benefits and risks for these women may be more favorable than in older women. Medical examination/follow-up:

Before initiating or reinstituting HRT, a complete personal and family medical history should be taken. Physical (including pelvic and breast) examination should be guided by this and by the contraindications and warnings for use. During treatment, periodic check-ups are recommended of a frequency and nature adapted to the individual woman. Women should be advised what changes in their breasts should be reported to their doctor or nurse (see 'Breast cancer' below). Investigations, including appropriate imaging tools, e.g mammography, should be carried out in accordance with currently accepted screening practices, modified to the clinical needs of the individual.

Overdose may cause nausea and vomiting and withdrawal bleeding may occur in some women. There are no specific antidotes and treatment should be symptomatic.

Drugs for menopausal symptoms: Hormone replacement therapy, Female Sex hormones

Store below 30°C and dry place. Keep away from light. Keep out of the reach of children.