16-alpha-Hydroxyestradiol

Uses

Atrophy of the lower urogenital tract related to oestrogen deficiency, notably

• For the treatment of vaginal complaints such as dyspareunia, dryness and itching
• For the prevention of recurrent infections of the vagina and lower urinary tract
• In the management of micturition complaints (such as frequency and dysuria) and mild urinary incontinence

Pre and postoperative therapy in postmenopausal women undergoing vaginal surgery.

Climacteric complaints such as hot flushes and night sweating.

A diagnostic aid in case of a doubtful atrophic cervical smear.

Infertility due to cervical hostility.

16-alpha-Hydroxyestradiol is also used to associated treatment for these conditions: Cervicitis, Menopausal and Postmenopausal Disorders, Hypoestrogenism, Estrogen Replacement Therapy

How 16-alpha-Hydroxyestradiol works

16-alpha-Hydroxyestradiol levels can be measured to give an indication of the general health of the fetus. DHEA-S is produced by the adrenal cortex of the fetus. This is converted to estriol by the placenta. If levels of "unconjugated estriol" are abnormally low in a pregnant woman, this may indicate a problem with the development of the child. The drug 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 estriol 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.

Dosage

16-alpha-Hydroxyestradiol dosage

Oral

It is important that the total daily dose is taken at one time. It may be taken with or without food.

Atropy of the lower urogenital tract: 4-8 mg/day for the first weeks, followed by a gradual reduction, based on relief of symptoms, until a maintenance dosage (e.g. 1-2 mg/day) isreached.

Pre and postoperative therapy in postmenopausal women undergoing vaginal surgery: 4-8 mg/day in the 2 weeks before surgery; 1-2 mg/day in the 2 weeks after surgery.

Climacteric complaints such as hot flushes and night sweating: 4-8 mg/day during the first weeks, followed by a gradual reduction. For maintenance therapy the lowest effective dosage should be used.

A diagnostic aid in case of a doubtful atrophic cervical smear: 2-4 mg/day for 7 days before taking the next smear.

Infertility due to cervical hostility: In general 1-2 mg/day on days 6-15 of the menstrual cycle. However, for some patients dosages as low as 1 mg/day are sufficient, whereas others may need up to 8 mg/day. Therefore, the dosage should be increased each month until an optimal effect on the cervical mucus is obtained.

Vaginalcream orpessary

Menopausal atrophic vaginitis: As 0.01% or 0.1% cream or 500 mcg pessary: Apply 500 mcg once daily, reduce to twice wkly subsequently.

Side Effects

Breast tension or pain, nausea, spotting, fluid retention and cervical hypersecretion may occasionally occur and be indicative of too high dosage. Headache, hypertension, leg cramps and vision disturbances are seldom observed. In general, most of these adverse reactions disappear after the 1 st week of treatment.

Breast enlargement, vaginal candidiasis, change in vaginal bleeding pattern, vomiting, stomach cramps, cholestatic jaundice, chloasma or melasma, erythema multiforme, erythema nodosum, hemorrhagic eruption, mental depression, chorea, increasing or decreasing body weight, edema, changes in libido.

Toxicity

ORAL (LD50): Acute: >2000 mg/kg [Rat].

Precaution

Thrombosis, severe liver disorders, porphyria, history during pregnancy or previous use of steroids of severe pruritus, cholestatic jaundice, herpes gestationis or otosclerosis. Lactation.

During prolonged treatment with estrogens, periodic medical examinations are advisable. With vaginal infections, a concomitant specific treatment is recommended. In order to prevent endometrial stimulation, the daily dose should not exceed 8 mg nor should this maximum dose be used for longer than several weeks. Patients with any of the following conditions should be monitored: A history of latent or overt cardiac failure, fluid retention due to renal dysfunction, hypertension, epilepsy or migraine (or a history of these conditions), severe liver disorders, endometriosis, fibrocystic mastopathy, porphyria, hyperlipoproteinaemia, a history during pregnancy or previous use of steroids of severe pruritus, cholestatic jaundice or herpes gestationis. Estrogen is reported to increase the risk of endometrial carcinoma in postmenopausal women. Use with precaution in gallbladder disorders, hypercalcemia, additional progestin, hypercoagulability, urethral bleeding and mastodynia.

Interaction

There are strong indications that estrogens, estriol included, can increase the pharmacologic effects of certain corticosteroids. If necessary, the dosage of the corticosteroid should be reduced. There are also some indications, mainly obtained with other estrogens or oral contraceptives, that concurrent use of estriol with activated charcoal, barbiturates, hydantoins and rifampicin may possibly decrease the effectiveness of estriol.

Pregnancy & Breastfeeding use

During pregnancy: 16-alpha-Hydroxyestradiol is contraindicated during pregnancy.

During lactation: Use 16-alpha-Hydroxyestradiol in breastfeeding women only if really needed, as estriol is excreted in the milk and it may decrease the quality and quantity of the milk production.

Contraindication

Pregnancy, Known or suspected estrogen-dependent tumours, undiagnosed vaginal bleeding, untreated endometrial hyperplasia, known or suspected breast cancer.

Acute Overdose

Symptoms that may occur in the case of an acute overdosage are nausea, vomiting and possibly withdrawal bleeding in females. No specific antidote is known. If necessary, a symptomatic treatment should be instituted

Storage Condition

Store in a dry & cool place protected from light & moisture. Keep out of reach of children.

Innovators Monograph

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