Estradiol Acetate Vaginal Ring - A Comprehensive Review

Overview:

The Food and Drug Administration (FDA) approved Estradiol acetate vaginal ring on August 10, 2018. Estradiol acetate significantly reduces symptoms like frequent hot flashes during the menopause phase in females. Common symptoms of menopause include irritation and dryness in the vagina and pain during intercourse. These common menopausal symptoms are relieved by Estradiol acetate vaginal ring. The vaginal ring is made up of plastic; it is soft in consistency and placed inside the vagina; the central core of the vaginal ring contains medications like Estradiol acetate. These vaginal rings release a continuous and fixed dosage of the drug that is instilled inside the vaginal ring. Thus, these vaginal rings serve as an excellent source for local drug delivery. Hence, it results in faster menopause symptom relief after installing vaginal rings containing Estradiol acetate.

Estradiol acetate is basically a substitute for estrogen hormone in hormone therapies. It functions by increasing the estrogen levels in women suffering from reduced levels of estrogen, as in the case of menopausal and postmenopausal females. Basically, Estradiol acetate functions by maintaining the female reproductive system. It acts as an agonist of estrogen receptors. Estradiol acetate is also considered a bioidentical or natural form of estrogen hormone.

What Are the Uses of Estradiol Acetate Vaginal Ring?

The most important use of the Estradiol acetate vaginal ring is to relieve menopausal symptoms. Symptoms like irritation and dryness in the vagina, as well as pain during intercourse, are relieved by Estradiol acetate vaginal ring. The purpose of these vaginal rings is to provide continuous local delivery for a given point in time.

Dosage and Administration:

Estradiol acetate vaginal ring is available in two strengths:

1. 0.05 mg/day: It contains 12.4 mg of equivalent Estradiol acetate and is released at the rate of 0.05 mg of Estradiol acetate per day for three months.

2. 0.10 mg/day: It contains 24.8 mg of equivalent Estradiol acetate and is released at the rate of 0.10 mg of Estradiol acetate per day for three months.

The following steps are to be followed for the administration of the Estradiol acetate vaginal ring:

1. Estradiol acetate vaginal ring is packed inside a pouch. This pouch has a tearing edge. Through this edge, the Estradiol acetate vaginal ring is taken out from the packaging pouch.

2. The patient is then asked to hold the ring in between the index finger.

3. The patient is asked to push the Estradiol acetate vaginal ring inside the vagina for constant release of the medication every day for the duration of three months.

Dosage Forms and Strengths:

Estradiol acetate vaginal ring is made up of silicon elastomer. The ring is available in the following dimensions:

• Outer diameter is approximately 56 mm, cross-sectional diameter is approximately 7.6 mm, and core diameter is noted to be 2 mm in Estradiol acetate vaginal ring available in the market.

Estradiol acetate vaginal ring is available in strengths of 0.05 mg/day and 0.10 mg/day.

Drug Interactions:

Anastrozole, a commonly prescribed aromatase inhibitor, Raloxifene, Tranexamic acid, and Tamoxifen are a few drugs that interact with Estradiol acetate in the vaginal rings and can alter their efficacy.

What Are the Adverse Reactions Associated With Estradiol Acetate Vaginal Ring?

• Allergy: Allergy to the drug Estradiol acetate as allergic patients may show symptoms of hypersensitivity reactions like angioedema (swelling affecting the tissue below the mucous membrane), anaphylaxis (acute allergic reaction), or exfoliative skin diseases (severe inflammation affecting the entire skin surface).

• Breast Tissue Changes: These include new lumps in the breast, redness, pain, and discharge from the breast.

• Gall Bladder Disorder: Symptoms of severe stomach pain, nausea, and vomiting are commonly noted as an adverse reaction associated with Estradiol acetate vaginal rings.

• Urinary Tract Infection: Urinary tract infection is noted in a few females, and the females prescribed Estradiol acetate vaginal rings are advised to maintain good hygiene to prevent such infections.

For Patients:

What Is Menopause?

Menopause is a non-pathological condition, which means it is not a disorder. Menopause, in simpler terms, states the cessation of the menstrual cycle in females for a period of twelve months. Menopause is associated with estrogen deficiency. The median age for females getting menopause is 51 years of age. Urogenital, as well as cardiovascular symptoms, are also noted in these individuals. As females age, their ovarian follicles start diminishing in numbers.

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) production increases in these females. The reduction in estrogen levels also disturbs the equilibrium of the hypothalamic-pituitary-ovarian cycle. All these factors, as mentioned above, fail in the development of the endometrial lining, and hence, the females start experiencing irregular periods, and the menstrual cycle stops altogether.

Other Causes of Menopause:

Hysterectomy is another common cause of menopause in females. A hysterectomy is a surgical procedure done to remove the uterus. Hysterectomy is usually prescribed in cases of heavy menstruation, prolapse of the uterus, pelvic pain, and cancer associated with the uterus.

What Is Estradiol Acetate Vaginal Ring?

Estradiol acetate vaginal ring is made up of silicon elastomer. The vaginal ring is a ring made up of plastic. It is soft in consistency and is placed inside the vagina; the central core of the vaginal ring contains medications like Estradiol acetate. Estradiol acetate is basically a substitute for estrogen hormone in hormone therapies. It functions by increasing the estrogen levels in women suffering from reduced levels of estrogen, as in the case of menopausal and postmenopausal females. Symptoms like irritation and dryness in the vagina, as well as pain during intercourse, are relieved by Estradiol acetate vaginal ring. The purpose of these vaginal rings is to provide continuous local delivery for a given point in time.

What Is the Most Significant Information That Should Be Known About Estradiol Acetate Vaginal Ring?

The drug should be judiciously prescribed.

• Females with frequent estrogen uptake history are at a higher risk of developing endometrial cancer. In such individuals, the addition of progestin has resulted in a reduced risk of endometrial cancer.

• Stroke and deep vein thrombosis are higher in menopausal females undergoing estrogen therapy. It is always advised to keep a check on blood pressure values and other parameters at regular intervals in these individuals.

• Symptoms like memory loss, increased irritability, and reduced social activities are associated with hormonal imbalances in females.

• Allergy to the drug Estradiol acetate as allergic patients may show symptoms of hypersensitivity reactions.

• Symptoms of severe stomach pain, nausea, and vomiting are commonly noted as adverse reactions associated with Estradiol acetate vaginal rings.

• Females prescribed Estradiol acetate vaginal rings are advised to maintain good hygiene to prevent such infections.

What Information Should Be Given to the Doctor Before Starting the Treatment With Estradiol Acetate Vaginal Ring?

Whenever an individual visits a doctor for the management of menopause symptoms, the following pieces of information should be given to the doctor:

• Family History: The patient should inform the doctor if any family members, like their parents, are suffering from diabetes mellitus (increased blood glucose levels), hypertension (increased blood pressure), hypotension, or renal and hepatic disorder. They should also disclose if their siblings or other family member has any history of underlying medical conditions. This information helps the doctors know the disorder's hereditary pattern and the common signs and symptoms that run in the individual's family. Family history of the disorder guides the doctor in planning a better management and treatment protocol.

• Personal History: Personal history includes altered symptoms that an individual faces, like excessive weight gain or weight loss, drowsiness, lethargy, swollen legs, increased heart rate, increased thirst, increased urge to eat food, and increased or reduced urination.

• Other Systemic Disorders: The patient should always inform the doctors if they are suffering from other underlying diseases like kidney disorders or liver dysfunction. Doctors prescribe medications, keeping in consideration the other underlying systemic conditions.

For Doctors:

Clinical Pharmacology:

The endogenous estrogen levels in the body maintain the female reproductive system and sexual characteristics. The ovarian follicle is the primary source of circulating estrogen in females.

Pharmacokinetics:

• Absorption: The drug delivery from Estradiol acetate vaginal rings is rapid for the first hours after administration. After that, the release of the drug is continuous and constant for the rest of the three months. Estradiol acetate vaginal rings drug delivery systems avoid first-pass metabolism; hence, the drug levels are constantly maintained.

• Distribution: The distribution process for exogenous estrogen is similar to that for endogenous estrogen. Estrogens circulate in the blood by binding themselves with other sex hormones.

• Metabolism: Estrogens undergo enterohepatic recirculation, and then the hormone gets reabsorbed. In postmenopausal females, a large amount of circulating estrogen is in the form of sulfate conjugates. These conjugates serve as a reservoir for the formation of active estrogen.

• Special Populations: Research has not been done on the impact of Estradiol acetate vaginal rings in patients suffering from renal and hepatic impairment.

What Are the Contraindications of Estradiol Acetate Vaginal Ring?

It is contraindicated in patients having the following conditions:

• Undiagnosed and abnormal or excessive genital bleeding in females.

• The females who are diagnosed with breast cancer have a history of breast cancer or are suspected of having breast cancer. Hormonal imbalance can occur in these individuals due to excess estrogen supplementation.

• Estradiol acetate vaginal ring should not be prescribed to females who are suffering from estrogen-associated tumors.

• Thromboembolic disorders (disorders associated with blood clots in the veins).

• Females with a history of allergic reactions or anaphylactic reactions are contraindicated from being prescribed this medication as the vaginal ring is composed of silicon, and many individuals are allergic to the silicon material.

• Individuals are suffering from liver disorders.

• Females who suspect pregnancy should never be prescribed Estradiol acetate vaginal ring as it may result in hormonal imbalance and miscarriage.

Warnings and Precautions:

1. Endometrial Cancer: Females with frequent estrogen uptake history are vulnerable to endometrial cancer. In such individuals, the addition of progestin has resulted in a reduced risk of endometrial cancer. So, in individuals who have abnormal genital bleeding, endometrial sampling should be done in intervals to rule out the chances of endometrial cancer or any other associated malignancy.

2. Cardiovascular Disorders: Stroke and deep vein thrombosis are higher in menopausal females undergoing estrogen therapy. It is always advised to keep a check on blood pressure values and other parameters at regular intervals in these individuals.

Following are a few of the features of heart failure that should be noted in these patients:

• Shortness of breath during exercising or while doing any other physical activity can also be present at rest in individuals suffering from heart failure.

• Fatigue and weakness are commonly noted, and the individual gets tired while performing basic day-to-day activities.

• Swellings in the legs, ankles, and feet are an important indicator of heart failure due to electrolyte imbalance in these individuals.

• Irregular heartbeat.

• Persistent cough and wheezing with whitish or pinkish-tinged mucus are also commonly noted in these individuals.

3. Dementia: It is commonly noted in females who are undergoing hormonal therapies. Symptoms like memory loss, increased irritability and reduced social activities. These psychological changes also affect the individual's ability to perform daily activities.

What Are the Drug Interactions of Estradiol Acetate Vaginal Ring?

• Aromatase inhibitor.

• Raloxifene.

• Tranexamic acid.

• Tamoxifen.