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 for the short term symptomatic treatment of vulvar and vaginal atrophy due to estrogen deficiency
  • 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;
  • adjust to the lowest effective dose which controls symptoms.
  • The administration should be cyclic (3 weeks on, 1 week off).
  • Intended for short term therapy.
  • The use of a progestin is recommended in postmenopausal women with a uterus.

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 to estrone and any component of the formula
• 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 data from the Women's Health Initiative (WHI) studies, an increased risk of invasive breast cancer was observed in postmenopausal women using conjugated estrogens (CE) in combination with medroxyprogesterone acetate (MPA).
  • This risk could be related to the duration of treatment and decreases after discontinuation of combined therapy.
  • A rise in abnormal mammogram findings was also reported when estrogen is used alone or in combination.
  • Postmenopausal women who had a hysterectomy using CE alone showed a lower risk of developing invasive breast cancer, regardless of their weight.
  • The risk of breast cancer was not significantly lower in high-risk women (family history of breast cancer, history of benign breast disease).

• Dementia

  • To prevent dementia, it is not a good idea to use estrogens without or with progestin.
  • The Women's Health Initiative Memory Study, (WHIMS), found that women aged 65 or older had a higher incidence of probable dementia when they took CE either alone or in combination of MPA.

• Endometrial cancer:

  • Endometrial cancer is more likely to occur in women who use unopposed estrogen.
  • To rule out malignancy in women who have undiagnosed abnormal vaginal blood flow, it is important to perform appropriate diagnostic tests, including endometrial sampling, if necessary.
  • A progestin may be added to estrogen therapy to reduce the risk of endometrial Hyperplasia, which is a precursor of endometrial carcinoma.
  • There is no evidence to suggest that natural estrogens have a different risk profile than synthetic estrogens of equivalent estrogen doses.
  • Endometrial cancer risk is dose- and duration-dependent. Risk appears to be highest with treatment for 5 years or more. It may also persist after discontinuation of therapy.
  • When low doses are being used locally to treat vaginal atrophy, a progestin may not be required.

• 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:

  • The risk of developing ovarian cancer in women who use estrogens postmenopausally, with or without progestins, may be increased. However, it is very rare.
  • Ovarian cancer is very rare. However, it is possible to develop in women who have a family history. Women should be counselled about 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]

  • To prevent heart disease, estrogens should not be combined with or without progestin.
  • Data from the Women's Health Initiative studies has shown that CE has an increased risk for stroke and deep vein thrombosis. There has also been a reported increase in DVT, stroke and pulmonary emboli (PE) in postmenopausal females between 50 and 79 years old.
  • 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.
  • Additional risk factors include diabetes mellitus, hypertension, SLE, obesity, hypercholesterolemia, tobacco use, and/or history of venous thromboembolism (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:

  • Women with hereditary angioedema may experience angioedema symptoms from exogenous estrogens.

• 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 routine physical examination that includes blood pressure and Papanicolaou smear, breast exam, mammogram.
• Monitor for signs of endometrial cancer in female patients with the uterus.
• Adequate diagnostic measures, including endometrial sampling, if indicated, should be performed to rule out malignancy in all cases of undiagnosed abnormal genital bleeding.

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:

• Assess need for therapy at 3 to 6 months of  intervals

Note: Monitoring of FSH and serum estradiol is not useful when managing vulvar and vaginal atrophy.

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.
• Patients should be lying on their back, the applicator should be inserted deeply into the vagina as far as it can go comfortably, pointing slightly downward.
• Following use, the applicator may be cleaned with mild detergent and warm water.
• Do not use hot water (may soften the plastic). The use of a progestin is recommended when administering estrogens to postmenopausal women with a uterus.

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 distributed; high concentrations in the sex hormone target organs

Protein binding:

• Bound to sex hormone-binding globulin and albumin

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.