Drug Monograph

Estriol Vaginal Cream

DESCRIPTION

Estriol Vaginal Cream is a vaginally administered steroid hormone.

HOW SUPPLIED

Estriol vaginal cream is available in a hypoallergenic base in following strengths:

  • Estriol 10mg/ml Vaginal Cream
CLINICAL PHARMACOLOGY

Estriol contains the natural female hormone estriol. Unlike other estrogens, estriol is short acting since it has only a short retention time in the nuclei of endometrial cells. It substitutes for the loss of estrogen production in menopausal women and alleviates menopausal symptoms.

Estriol is particularly effective in the treatment of urogenital symptoms. In case of atrophy of the lower urogenital tract estriol induces the normalization of the urogenital epithelium and helps to restore the normal microflora and the physiological pH in the vagina. As a result, it increases the resistance of the urogenital epithelial cells to infection and inflammation reducing vaginal complaints such as dyspareunia, dryness, itching, vaginal and urinary infections, micturition complaints and mild urinary incontinence.

CLINICAL EVIDENCE

• In an open, prospective, multicenter, controlled study, 629 women suffering from stress and urgency urinary incontinence were treated with vaginally estriol at a dose of 10 mg daily for 3 weeks, and 10mg twice weekly for another 3 weeks. Of the 629 women who started the study, 552 were available for follow-up after 6-weeks of treatment. Subjective improvements in symptoms of stress urinary incontinence (SUI) were 82% for grade 1, 77% for grade 2, and 69% for grade 3. Voluntary urinary control and symptoms of urgency were improved in more than 80% of patients, and frequency was reduced in almost 50% of women. Compared with conditions at the outset of the study, after 6 weeks, vaginal lubrication was normalized in 77%, and intercourse was no longer painful for 88% of women.1

INDICATIONS AND USAGE

Estriol Vaginal Cream has been studied in women for the treatment of postmenopausal stage I, stage II, and stage III urinary incontinence.1

DOSING AND ADMINISTRATION

Administer 10mg Estriol vaginal cream daily at bedtime 3 times weekly.

DRUG INTERACTIONS

No examples of interactions between Estriol and other medicines have been reported in clinical practice. Although data are limited, interactions between Estriol and other medicinal products may occur. The following interactions have been described with use of combined oral contraceptives which may also be relevant for Estriol.

The metabolism of estrogens may be increased by concomitant use of substances known to induce drug-metabolizing enzymes, specifically cytochrome P450 enzymes, such as anticonvulsants (e.g. hydantoins (phenytoin), barbiturates (phenobarbital), carbamazepine), anti-infectives (e.g. griseofulvin, rifamycins (rifampicin, rifabutin), and antiretroviral agents (nevirapine, efavirenz)).

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Herbal preparations containing St John’s wort (Hypericum Perforatum) may induce the metabolism of oestrogens.

Clinically, an increased metabolism of estrogens may lead to decreased effect and changes in the uterine bleeding profile. Estriol may possibly increase the pharmacological effects of corticosteroids, succinylcholine, theophyllines and troleandomycin.

ADVERSE EFFECTS

From literature and safety surveillance monitoring, the following adverse reactions have been reported for estriol.

  • Fluid Retention
  • Nausea
  • Breast discomfort and pain
  • Postmenopausal spotting
  • Cervical Discharge
  • Application site irritation and pruritis
  • Flu like symptoms
WARNINGS AND PRECAUTIONS

Current or Past History of Breast Cancer. Use of exogenous estrogen is contraindicated in women with a known or suspected history of breast cancer.

USE IN SPECIFIC POPULATION
Pregnancy

Estriol is contraindicated during pregnancy. If pregnancy occurs during medication with Estriol, treatment should be withdrawn immediately. The results of most epidemiological studies to date relevant to inadvertent fetal exposure to estrogens indicate no teratogenic or fetotoxic effects.

Lactation

Estriol is not indicated during lactation. Estriol is excreted in breast milk and may decrease milk production.

PHARMACOKINETICS
Absorption

Intravaginal administration of estriol ensures optimal availability at the site of action. Estriol is also absorbed into the general circulation, as is shown by a sharp rise in the plasma levels of unconjugated estriol.

Distribution

Peak plasma levels are reached 1-2 hours after application. After vaginal application of 0.5 mg estriol, Cmax is approximately 100 pg/ml, Cmin is approximately 25 pg/ml and Caverage is approximately 70 pg/ml. After 3 weeks of daily administration of 0.5 mg vaginal estriol, Caverage has decreased to 40 pg/ml.

Metabolism

Nearly all (90%) estriol is bound to albumin in the plasma and in contrast with other estrogens, hardly any estriol is bound to sex hormone-binding globulin (SHBG). The metabolism of estriol consists principally of conjugation and deconjugation during the enterohepatic circulation.

Elimination

Estriol, being a metabolic end product, is mainly excreted via the urine in the conjugated form. Only a small part (±2 %) is excreted via the feces, mainly as unconjugated estriol.

TOXICITY
ESTRIOL

The acute toxicity of estriol in animals is very low. Overdosage with Estriol cream after vaginal administration is unlikely. However, in cases where large quantities are ingested, nausea, vomiting and withdrawal bleeding in females may occur. No specific antidote is known. Symptomatic treatment can be given if necessary.

STORAGE

Store at room temperature.

REFERENCES
  1. Schmidbauer CP. Vaginale Ostriolapplikation zur Behandlung der postmenopausalen Harninkontinenz [Vaginal estriol administration in treatment of postmenopausal urinary incontinence]. Urologe A. 1992;31(6):384-389
  2. Schulte-Uebbing C, Schlett S, Craiut D, Bumbu G. Stage I and II Stress Incontinence (SIC): High dosed vitamin D may improve effects of local estriol. Dermatoendocrinol. 2016;8(1)
  3. Crescioli C, Morelli A, Adorini L, et al. Human bladder as a novel target for vitamin D receptor ligands. J Clin Endocrinol Metab. 2005;90(2):962-972. doi:10.1210/jc.2004-1496
  4. Bischoff HA, Borchers M, Gudat F, et al. In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Histochem J. 2001;33(1):19-24.
  5. Badalian SS, Rosenbaum PF. Vitamin D and Pelvic Floor Disorders in Women: Results From the National Health and Nutrition Examination Survey. Obstetr Gynecol. 2010;115(4):795–803.
  6. Vaughan CP, Johnson TM, II, Goode PS, Redden DT, Burgio KL, Markland AD. Vitamin D and lower urinary tract symptoms among US men: results from the 2005–2006 National Health and Nutrition Examination Survey. Urology. 2011;78(6):1292–7.
  7. Navaneethan PR, Kekre A, Jacob KS, Varghese L. Vitamin D deficiency in postmenopausal women with pelvic floor disorders. J Mid-life Health. 2015;6(2):66–9.
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