Estrone (Estragyn) is a type of estrogen that is used for topical application for the treatment of vaginal dryness and atrophy.

Estrone (Estragyn) Uses:

Note: Not approved in the US

• Vulvar and vaginal atrophy:

  • Used to alleviate the short-term symptoms of vulvar and vaginal atrophy brought on by a lack of oestrogensed to alleviate the short-term symptoms of vulvar and vaginal atrophy brought on by a lack of oestrogen
  • Limitations of use: To be prescribed with an appropriate progestin in women with a uterus.

Estrone (Estragyn) Vaginal Cream Dose in Adults

Estrone (Estragyn) Vaginal Cream Dose in the treatment of Vulvar and vaginal atrophy:

• Intravaginal:
  • Insert 0.5 to 4 g once in  a day;
  • Choose the lowest dose that still effectively manages symptoms.
  • The dosage should be repeated periodically (3 weeks on, 1 week off).
  • Intended as an acute form of therapy.
  • Progestin usage is advised for postmenopausal women who still have uteruses.hoose the lowest dose that still effectively manages symptoms.
  • The dosage should be repeated periodically (3 weeks on, 1 week off).
    intended as an acute form of therapy.
  • Progestin usage is advised for postmenopausal women who still have uteruses.

Use in Children:

Not indicated.

Estrone (Estragyn) Pregnancy Risk Category: X

• It is not recommended for women who are pregnant or have a suspicion of being pregnant.

Estrone use during breastfeeding:

• Breastfeeding women should not use it.

Estrone (Estragyn) Dose in Kidney Disease:

The manufacturer’s labeling doesn't provide any dosage adjustments (has not been studied); use with caution.

Estrone (Estragyn) Dose in Liver disease:

Its use is contraindicated in active hepatic dysfunction or disease.

Side effects of Estrone (Estragyn):

• Cardiovascular:

  • Chest Pain
  • Edema
  • Increased Blood Pressure
  • Syncope
  • Thromboembolic Disease
  • Cerebrovascular Accident
  • Thrombophlebitis
  • Venous Thromboembolism

• Central Nervous System:

  • Aphasia
  • Depression
  • Loss Of Consciousness
  • Migraine
  • Dizziness
  • Exacerbation Of Epilepsy
  • Exacerbation Of Migraine Headache
  • Headache
  • Numbness Of Extremities
  • Paralysis

• Endocrine & Metabolic:

  • Decreased Glucose Tolerance
  • Exacerbation Of Porphyria
  • Lipid Metabolism Disorder
  • Fluid Retention
  • Hypothyroidism
  • Increased Serum Glucose

• Gastrointestinal:

  • Abdominal Pain
  • Vomiting
  • Gallbladder Disease
  • Nausea

• Genitourinary:

  • Abnormal Vaginal Hemorrhage
  • Breakthrough Bleeding
  • Exacerbation Of Endometriosis
  • Breast Swelling
  • Breast Tenderness
  • Endometrial Hyperplasia
  • Spotting

• Hematologic & Oncologic:

  • Endometrial Carcinoma
  • Uterine Fibroids (Increase In Tenderness/Pain)
  • Enlargement Of Uterine Fibroid
  • Malignant Neoplasm Of Ovary

• Hepatic:

  • Cholestatic Jaundice
  • Exacerbation Of Hepatic Hemangioma

• Hypersensitivity:

  • Angioedema

• Neuromuscular & Skeletal:

  • Osteosclerosis

• Ophthalmic:

  • Visual Disturbance

• Respiratory:

  • Hemoptysis

Contraindications to Estrone (Estragyn):

• Hypersensitivity 
• Undiagnosed abnormal Genital Bleeding;
• DVT or PE (current and/or historical of);
• Active or past arterial thromboembolic diseases (eg stroke, MI) or active and chronic thrombophlebitis.
• Estrogen-dependent tumor (known and suspected);
• Breast cancer (known, suspected, or history of);
• progestin dependent malignant tumor (eg, endometrial cancer);
• Endometrial hyperplasia
• Hepatic impairment or disease
• Ophthalmic vascular diseases can cause vision loss, partial or total.
• Classic migraine
• Breast-feeding
• pregnancy.

Warnings and precautions

• Bone disease:

  • Patients with malignant and metabolic bone disease that is associated with hyperglycemia should be cautious.
  • Extended estrogen use with or without progestin may affect calcium and phosphorus metabolism.

• Breast cancer: [Canadian boxed warning]

  • Based on information from the Women's Health Initiative (WHI) research, postmenopausal women using conjugated estrogens (CE) in conjunction with medroxyprogesterone acetate had a higher chance of developing invasive breast cancer (MPA).
  • This risk may be correlated with the length of therapy and declines with the cessation of combined therapy.
  • When oestrogen is administered alone or in combination, there has also been a reported increase in abnormal mammography findings.
  • Regardless of their weight, postmenopausal women who underwent a hysterectomy using CE alone had a decreased chance of developing invasive breast cancer.
  • In high-risk women, the risk of breast cancer was not noticeably decreased (family history of breast cancer, history of benign breast disease).

• Dementia

  • Using estrogens alone or in combination with progestin is not recommended for preventing dementia.
  • According to the Women's Health Initiative Memory Study (WHIMS), women over 65 who used CE alone or in combination with
  • MPA had a greater risk of probable dementia.

• Endometrial cancer:

  • When oestrogen is not countered, endometrial cancer is more likely to develop in females.
  • It is crucial to carry out the proper diagnostic procedures, including endometrial sampling, if required, in order to rule out cancer in women who have undetected irregular vaginal blood flow.
  • To lower the risk of endometrial Hyperplasia, a precursor to endometrial cancer, a progestin may be added to oestrogen therapy.
    In comparison to synthetic estrogens with identical oestrogen dosages, there is no evidence to imply that natural estrogens have a different risk profile.
  • The risk of endometrial cancer is dose- and time-dependent. With treatment for five years or longer, risk appears to be at its maximum. Additionally, it could continue even if therapy is stopped.
  • A progestin may not be necessary when low dosages of local medication are used to treat vaginal atrophy.

• Endometriosis:

  • Estrogens may exacerbate endometriosis.
  • Women with endometrium after hysterectomy should consider adding a progestin.
  • Post-hysterectomy with estrogen therapy unopposed has led to malignant transformation of the remaining endometrial implants.

• Hypertension:

  • Monitor for an increase in blood pressure.

• Heir to thrombophilia

  • Women who have inherited thrombophilia (eg protein C or S deficiencies) might be at greater risk for venous embolism.

• Ovarian cancer:

  • Women who use oestrogen postmenopausally, with or without progestins, may have a higher chance of developing ovarian cancer. It is extremely uncommon, though.
  • Ovarian cancer is quite uncommon. However, it is conceivable for women with a family history to develop it. Women need to receive counselling over this association.
  • Although the results of different studies may not be consistent, it appears that there is no significant risk associated with therapy's duration, route or dosage.
  • One study found that the risk of developing cancer after discontinuing therapy for 2 years was lower in patients who had stopped taking it.

• Asthma

  • Asthma can be exacerbated by taking care.

• Carbohydrate intolerance:

  • This may cause impaired glucose tolerance.

• Cardiovascular disease: [Canadian boxed warning]

  • Estrogens shouldn't be used with progestin or without it to prevent heart disease.
  • According to data from the Women's Health Initiative research, CE increases the risk of deep vein thrombosis and stroke. In postmenopausal females aged 50 to 79, there has also been a reported rise in DVT, stroke, and pulmonary emboli (PE).
  • You should manage your risk factors well. If you suspect that adverse cardiovascular events may occur, stop using the medication immediately.
  • Women with DVT/PE (or a history thereof) and women with an active or recent arterial disease (stroke or MI) are contraindicated.
  • Diabetes mellitus, hypertension, SLE, obesity, hypercholesterolemia, smoking, and/or a history of venous thromboembolism are additional risk factors (VTE).

• Cerebrovascular Insufficiency

  • If classical migraine, loss consciousness, paralysis or visual disturbances, discontinue use

• Fluid retention can lead to more severe diseases

  • Fluid retention can exacerbate certain diseases, such as renal dysfunction or cardiac problems.

• Epilepsy:

  • Epilepsy can be aggravated if you are careful.

• Fibroids:

  • Patients with fibroids (leiomyomata) should be treated with caution
  • Stop using fibroids if you experience sudden swelling, pain, tenderness, or enlargement.

• Gallbladder disease

  • Postmenopausal estrogen use may increase the risk of gallbladder diseases that require surgery.

• Hepatic hemomangiomas

  • Be careful with hepatic hemomangiomas. They can worsen the condition.

• Hepatic dysfunction

  • Patients with hepatic dysfunction are less likely to be able to metabolize estrogens.
  • Discontinue if jaundice develops.
  • If liver function tests are not normal, use is prohibited.
  • Be cautious if you have a history of biliary or liver problems.

• Hereditary angioedema:

  • Exogenous estrogens may cause angioedema symptoms in women with hereditary angioedema.

• Otosclerosis

  • Patients with otosclerosis should exercise caution.

• Porphyria

  • Patients with porphyria should be cautious.

• Renal impairment

  • Patients with impaired renal function should be cautious.

• SLE:

  • SLE can exacerbate the condition so be careful.

Estrone: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• A  standard physical checkup that includes a mammography, breast exam, Papanicolaou smear, and blood pressure checks.
• In female patients with uterus, look out for indications of endometrial cancer.
• In all cases of undetected abnormal vaginal bleeding, adequate diagnostic procedures should be carried out, including endometrial sample, if necessary, to rule out cancer.

Monitor for:

• loss of vision, sudden onset of proptosis, diplopia, migraine;
• signs and symptoms of thromboembolic disorders;
• lipid profiles in patients being treated for hyperlipidemias;
• glycemic control in patients with diabetes;
• thyroid function in patients on thyroid hormone replacement therapy.

Menopausal symptoms, vulvar, and vaginal atrophy:

• Examine the need for counselling every three to six months.

Note: The management of vulvar and vaginal atrophy does not benefit from the monitoring of FSH and serum estradiol.

How to use Estrone (Estragyn) vaginal cream?

• Administer intravaginally with the provided calibrated applicator at the same time each day at a time convenient to the patient's schedule.
• The applicator should be put into the vagina as deeply as it can go comfortably while the patient is resting on their back. It should be angled slightly downward.
• The applicator can be washed with warm water and mild detergent after use.
• Avoid using boiling water (may soften the plastic). When giving oestrogen to postmenopausal women with uteruses, a progestin should be used.

Mechanism of action of Estrone (Estragyn):

• Estradiol, the main intracellular human estrogen, is also the primary estrogen secreted before menopause.
• Estrone production is higher after menopause. Vaginal estrone can replace the lower endogenous estrone levels and alleviate symptoms of vulvovaginal dysplasia.

Absorption:

• Readily

Distribution:

• Widely present; highly concentrated in the organs that sex hormones target.

Protein binding:

• Albumin and sex hormone-binding globulin

Metabolism:

• Hepatic; no first-pass metabolism via vaginal administration, but undergoes enterohepatic uptake and recycling

Excretion:

• Urine

International Brand Names of Estrone:

• Estragyn

Estrone Brand Names in Pakistan:

There is no brand available in Pakistan.