Actions of Oestring in details
Pharmacotherapeutic Group: Estrogens (genitourinary system and sexual hormones). ATC Code: G03CA03.
Pharmacology: Pharmacodynamics: Oestring gel belongs to the group of natural, physiological estrogens. The active ingredient is chemically and biologically identical to human endogen Oestring. The pharmaceutical form enables the systemic administration of 17β-Oestring by applying it to healthy skin. Oestring gel substitutes for the loss of estrogen production in postmenopausal or ovariectomised women.
The most active form of estrogen is Oestring which is mainly produced by the ovarian follicles throughout the childbearing period of women's life.
The transdermal administration of Oestring gel enables to avoid the hepatic first-pass effect which induces an increase in the synthesis of angiotensin, very low density lipoproteins (VLDL) (triglycerides) and certain coagulation factors.
Pharmacokinetics: Pharmacokinetic studies indicate that when applied topically to a large area of skin in a volatile solvent, approximately 10% of the Oestring is percutaneously absorbed into the vascular system regardless of the age of the patient. Daily application of Oestring 2.5 or 5 g over a 400-750 cm2 surface area results in a gradual increase in estrogen blood levels to steady-state after approximately 3-5 days and provides circulating levels of both Oestring and estrone equivalent in absolute concentration and their respective ratio to those obtained during the early-mid follicular phase of the menstrual cycle.
Oestring was administered to 17 postmenopausal women once daily on the posterior surface of 1 arm from wrist to shoulder for 14 consecutive days.
Maximum serum concentrations (Cmax) of Oestring and estrone on day 12 were 117 pg/mL and 128 pg/mL, respectively. The time-averaged serum Oestring and estrone concentrations (Caverage) over the 24-hr dose interval after administration of Oestring 2.5 g on day 12 were 76.8 pg/mL and 95.7 pg/mL, respectively.
Metabolism of Oestring takes place mainly in the liver under estriol, estrone and their conjugated metabolites (glucuronides, sulphates). These metabolites also undergo enterohepatic recirculation.
When treatment is discontinued, Oestring and urinary conjugated Oestring concentrations return to baseline in about 76 hrs.
Toxicology: Preclinical Safety Data: Long-term continuous administration of estrogen, with and progestin in women, with and without a uterus, has shown an increase risk of endometrial, breast and ovarian cancer.
Long-term, continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis and liver.
How should I take Oestring?
Take Oestring exactly as it was prescribed for you. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.
Oestring may increase your risk of developing a condition that may lead to uterine cancer. Your doctor may prescribe a progestin to take while you are using Oestring, to help lower this risk. Report any unusual vaginal bleeding right away.
Your doctor should check your progress on a regular basis (every 3 to 6 months) to determine whether you should continue this treatment. Self-examine your breasts for lumps on a monthly basis, and have regular mammograms while using Oestring.
If you need surgery or medical tests or if you will be on bed rest, you may need to stop using this medicine for a short time. Any doctor or surgeon who treats you should know that you are using Oestring.
Store at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.
Oestring administration
Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
Apply the skin patch to clean, dry skin on your stomach, lower back, or buttocks. Choose a different spot within these skin areas each time you apply a new patch. Avoid skin that is oily, irritated, or damaged.
Press the patch in place firmly for about 10 seconds, especially around the edges.
Do not apply a skin patch to your breasts. Do not apply a patch where it might be rubbed off by tight clothing, such as under an elastic waistband.
If a patch falls off, try putting it back on to a different skin area, pressing the patch into place for 10 seconds. If the patch will not stick you may apply a new one.
If you need surgery or medical tests or if you will be on bed rest, you may need to stop using this medication for a short time. Any doctor or surgeon who treats you should know that you are using Oestring.
Your doctor should check your progress on a regular basis (every 3 to 6 months) to determine whether you should continue this treatment. Self-examine your breasts for lumps on a monthly basis while using Oestring transdermal.
The Oestring transdermal patch may burn your skin if you wear the patch during an MRI (magnetic resonance imaging). Remove the patch before undergoing such a test.
Store at room temperature away from moisture and heat.
Oestring pharmacology
Estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, Oestring is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 µg of Oestring daily, depending on the phase of the menstrual cycle. After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women.
Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) through a negative feedback mechanism, and estrogen replacement therapy acts to reduce the elevated levels of these hormones seen in postmenopausal women.
Pharmacokinetics
The pharmacokinetics of transdermally administered Oestring using Oestring (Oestring transdermal) have been evaluated in a total of 138 healthy postmenopausal women in 9 clinical pharmacology and biopharmaceutic studies.
Absorption
Transdermal administration of Oestring produces therapeutic serum concentrations of Oestring with lower circulating concentrations of estrone and estrone conjugates and requires smaller total doses than does oral therapy.
The in vivo Oestring daily delivery rate from Oestring (Oestring transdermal) was estimated using the baseline adjusted average serum concentrations determined from pharmacokinetic studies and an Oestring clearance value of 1600 L/day. The estimated mean in vivo transdermal delivery rates of Oestring are 0.020 mg/day, 0.051 mg/day, and 0.101 mg/day for the 11 cm,number of subjects
Excretion
Oestring, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates. Serum concentrations of Oestring and estrone returned to baseline values within 12 to 24 hours after removal of Oestring (Oestring transdermal).
Special Populations
No specific studies have been conducted using Oestring (Oestring transdermal) in any special populations.
Drug Interactions
No specific drug interaction studies have been conducted using Oestring (Oestring transdermal).
Clinical Trials
In a 12-week, double-blind study evaluating the efficacy and safety of Oestring (Oestring transdermal) 0.025, 0.05, and 0.1 versus placebo in symptomatic women (average of 8 or more moderate to severe hot flushes per day), reduction in the frequency of these vasomotor symptoms was demonstrated within 4 weeks. Results from this trial are presented in Table 4 and Figure 4.
After 4 weeks of treatment, the mean reduction in the moderate to severe vasomotor symptoms (MSVS) was up to 8.6 MSVS per day in the Oestring (Oestring transdermal) 0.025 group, 9.2 and 10.2 in the Oestring (Oestring transdermal) 0.05, and Oestring (Oestring transdermal) 0.1 groups respectively, compared with 5.3 in the placebo group. After 12 weeks of treatment, this increased to 9.9 in the Oestring (Oestring transdermal) 0.025 group, 10.4 in the Oestring (Oestring transdermal) 0.05 group, and 10.7 in the Oestring (Oestring transdermal) 0.1 group and remained stable at 5.2 in the placebo group.
| Table 4: Changes From Baseline in Frequency of MSVS | ||||
| Week | Placebo (N=54) | Oestring 0.025 mg/day (N=48) | Oestring 0.05 mg/day (N=47) | Oestring 0.1 mg/day (N=47) |
Week 0 (Baseline) Mean ± SD | 11.4 ± 3.7 | 11.6 ± 5.4 | 10.9 ± 4.2 | 11.2 ± 2.8 |
| Week 4 Mean Reduction ± SD(% Reduction) | -5.3 ± 4.1 (-48.9%) | -8.6 ± 5.7* (-72.6%) | -9.2 ± 4.5* (-84.4%) | -10.2 ± 2.9* (-92.0%) |
| Week 8 Mean Reduction ± SD(% Reduction) | -5.5 ± 4.7 (-51.5%) | -9.4 ± 5.7* (-79.8%) | -10.3 ± 4.3* (-94.0%) | -10.6 ± 2.8* (-95.4%) |
| Week 12 Mean Reduction ± SD(% Reduction) | -5.2 ± 5.1 (-50.3%) | -9.9 ± 5.8* (-83.4%) | -10.4 ± 4.2* (-95.3%) | -10.7 ± 2.8* (-95.6%) |
*Statistically different from placebo in mean reduction (Dunnett’s test) |
Figure 4: Reduction of MSVS During Double-Blind, Placebo-Controlled Study
Maintenance of the relief of VMS over a median period of 2 years was documented in 2 open-label trials.
References
- DailyMed. "ESTRADIOL HEMIHYDRATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- NCIt. "Therapeutic Estradiol: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
- EPA DSStox. "17beta-Estradiol: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
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Information checked by Dr. Sachin Kumar, MD Pharmacology
